bluuebunny/crossref_metadata_2025 huggingface dataset:
Telomere length analysis in monocytes and lymphocytes from patients with systemic lupus erythematosus using multi-color flow-FISH
Authors: Beier F. , Balabanov S. , Amberger C.C. , Hartmann U. , Manger K. , Dietz K. , Kötter I. , Brummendorf T.H.
Published: November 2007

In order to analyse telomere length in subsets of human peripheral blood lymphocytes and monocytes, we modified a recently developed multicolor flow- fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and antibody staining for cell surface antigens. We analysed telomere length of peripheral blood mononuclear cells in a group of 22 patients with systemic lupus erythematosus (SLE) and 20 age-matched healthy donors. We found that neither CD4+, CD8+, CD19+ cells nor CD14+ monocytes have significantly shorter telomeres compared with their healthy counterparts. On the basis of these findings, we then used monocyte telomere length as internal reference in order to control for intra-individual variability in telomere length. By using this approach, we could demonstrate significant telomere shortening in all three lymphocyte subsets (in all cases P < 0.05) compared with monocytes. However, these differences did not vary significantly between SLE patients and controls. In summary, telomere lengths in subpopulations of hematopoietic cells can be monitored in patients with SLE using multicolor flow-FISH. While confirming data by other groups on telomere length in lymphocyte subpopulations, our data argue against an increased proliferation rate of peripheral blood monocytes reflected by accelerated telomere shortening in patients with SLE. Lupus (2007) 16, 955—962.
The Outcome of Pregnancy in Women with Lupus Nephritis
Authors: Oviasu Efosa , Hicks Jackie , Cameron J. Stewart
Published: November 2007

We analysed the outcome of pregnancy in patients with pre-existing lupus nephritis, seen in a tertiary referral centre for nephrology. Fifty-three pregnancies in 25 patients who already had clinical and histological evidence of lupus nephritis were recorded between January 1970 and June 1989, and data were analysed retrospectively. All 53 pregnancies occurred in patients with more or less stable disease, while three pregnancies during which lupus first presented were excluded. Six pregnancies were ended by therapeutic abortions (four for social reasons), and in eight spontaneous abortion occurred. Thus, 39 deliveries occurred, 28 at 36 weeks or more, while 11 were delivered prematurely, of which one was a stillbirth. After allowance was made for therapeutic abortions, the fetal loss rate (9/47) was 19%. Seventeen Caesarian sections were performed in the 39 completed pregnancies (44%), 11 as emergencies. Although the overall fetal loss, incidence of premature births and Caesarian section rate were all higher than expected for a population of normal women, neither initial histology, treated hypertension, the presence of proteinuria or a nephrotic syndrome showed statistically significant relationships with the outcome of completed pregnancies. In no case was maternal renal function affected irreversibly, although proteinuria increased substantially during pregnancy in six patients, and creatinine clearance fell during pregnancy, also in six patients. No 'flares' in systemic disease were seen, but all patients save five were treated with a brief period of high-dose oral corticosteroids or intravenous methylprednisolone in the postpartum period. No case of neonatal lupus or congenital heart block was observed. Pregnancy in patients with stable lupus nephritis established on treatment usually has a good outcome, even in the presence of initially severe disease, persisting treated hypertension, and continued immunosuppression with prednisolone and azathioprine, although a higher fetal loss is observed. The outcome for patients with lupus and even severe nephritis is no worse than that previously reported in women with lupus without nephritis.
Parvovirus B19 Infection Can Induce Histiocytic Necrotizing Lymphadenitis (Kikuchi's Disease) Associated with Systemic Lupus Erythematosus
Authors: Meyer O. , Kahn M.F. , Grossin M. , Ribard P. , Belmatoug N. , Morinet F. , Fournet J.C.
Published: November 2007

We report three cases of systemic lupus erythematosus (SLE) associated with necrotizing histiocytic lymphadenitis (Kikuchi's disease) and immunologically proven human parvovirus B19 infection. Simultaneous occurrence of SLE and Kikuchi's disease was a characteristic of the three cases. Kikuchi's disease is an uncommon disease that usually affects young women and is characterized by painless unilateral cervical lymph-node enlargement. T-cell regions of affected lymph nodes are exclusively involved with patchy paracortical necrosis surrounded by a polymorphous cell population of histiocytes and macrophages. However, lymphadenopathy in patients with SLE may be histologically indistinguishable from Kikuchi's necrotizing lymphadenitis. The cause of Kikuchi's remains uncertain, although infectious agents have been proposed. A positive IgM-specific anti-human parvovirus B19 antibody test in our three cases suggests that B19 can induce a necrotizing histiocytic lymphadenitis and possibly a clinical SLE flare. High-dose (1 mg/kg/day) and medium-dose (0.5 mg/kg/day) oral prednisone was an effective treatment for constitutional and visceral symptoms of Kikuchi's and SLE diseases.
The Long-Term Clinical Outcome of 56 Patients with Biopsy-Proven Lupus Nephritis Followed at a Single Center
Authors: Derksen Ronald H.W.M. , Hené Ronald J. , Kater Louis
Published: November 2007

We retrospectively evaluated the clinical outcome of 45 female and 11 male patients with biopsy-proven lupus nephritis, followed at our hospital between February 1974 and February 1990. In the majority signs of nephritis were present at the time systemic lupus erythematosus was diagnosed (range: —42-156 months) and the median time from onset of nephritis to biopsy was 2 months. The median follow-up from the time of the biopsy was 53.5 months (range: 2-192), the median age at biopsy 25 years and the median serum creatinine level 1.2 mg/dl. Initial renal biopsies had the following histopathological classes according to the World Health Organization criteria (n): I (2); II (10); III (10); IV (28); V (5); VI (1). Over the study period active episodes were treated with high-dose oral prednisone alone or combined with intravenous nitrogen mustard and oral chlorambucil (1974-75), azathioprine (1978-86), cyclophosphamide (1986-90) and/or plasma-exchange (1976-84). These strategies were based on literature data or multicenter studies in which we participated.

Eight patients developed end-stage renal disease (ESRD) (median: 47 months post-biopsy; range: 20-120). In these, initial biopsies showed class IV in seven, and class V in one. Confounded risk factors for ESRD were class IV biopsy, male gender and serum creatinine level above 1.4 mg/dl. The calculated proportion without ESRD 5 years post-biopsy was 87% (95% confidence limits: 98-76%), and at 10 years 70% (95% confidence limits: 90-49%). Five patients (11.2%) died; causes of death were cerebrovascular accident (n = 2), cerebral lupus (n = 2) and S. aureus sepsis (n = I). Twelve (21.4%) patients had localized herpes zoster infection; six (10.7%) had a salmonella sepsis.
Observations on the Interleukin-6 and Acute Phase Protein Profiles in the Disease Course of Patients with Lupus Erythematosus
Authors: Swaak A.J.G. , Sintnicolaas C. , Meijer C. , Smeenk R.T.
Published: November 2007

In vitro models have shown that interleukin-6 (IL-6) is the main dominator of the stimulation of the full spectrum of acute phase proteins. This study describes IL-6 levels in relation to levels of acute phase proteins in 15 systemic lupus erythematosus (SLE) patients, with special atten tion given to those patients with increased serum levels of IL-6. Three episodes with elevated levels of IL-6 were observed in a period shortly after a flare-up of SLE, in three of the 15 patients. In one of these three patients a clear increase in the C-reactive protein (CRP) level, preceded by an IL-6 increase, was observed. In the other two patients, CRP levels remained unchanged. It is speculated that, next to IL-6, another signal is operative or needed for the start of an acute phase reaction. However, influences of the disease itself or of the administered therapy cannot be excluded as the cause of the described discrepancy between IL-6 and acute phase protein profiles in these two SLE patients.
Antiganglioside Antibodies in Patients with Neuropsychiatric Systemic Lupus Erythematosus
Authors: Pereira  , Yoshinari Natalino H. , De Oliveira Ricardo M. , Cossermelli Wilson
Published: November 2007

Antiganglioside antibodies (AGA) were determined in sera and cerebrospinal fluids (CSF) from 50 systemic lupus erythematosus (SLE) patients, and age-matched normal controls. The SLE patients were subdivided according to the type of clinical manifestation into two groups: neuropsychiatric SLE and active SLE without neuropsychiatric manifestation.

The presence of these antibodies showed a significant correlation between IgG AGA in the CSF and IgM AGA in the serum and neuropsychiatric SLE. Fifteen patients had this antibody in the CSF without detectable levels in the serum. No correlation was seen between anti cardiolipin antibodies in the serum or CSF and neuropsychiatric SLE.

The present work suggests that antibodies against gangliosides may be a marker for neuro psychiatric SLE and that intrathecal antibody production can result in the development of this manifestation.
Plasma Sex Hormones and Aromatase Activity in Tissues of Patients with Systemic Lupus Erythematosus
Authors: Folomeev Mikhail , Dougados Maxime , Beaune Joelle , Kouyoumdjian Jean-Clod , Nahoul Khalil , Amor Bernard , Alekberova Zemfira
Published: November 2007

Clinical observations and experimental data suggest that sex hormones influence the develop ment of systemic lupus erythematosus (SLE). An imbalance between androgen and estrogen plasma levels may suggest an abnormality in the aromatase activity involved in estradiol syn thesis. Aromatase activity in skin and subcutaneous tissue and plasma sex-hormone levels (testosterone, androstenedione, estrone, estradiol, dehydrosterone sulfate, cortisol) were measured in 15 SLE patients (nine female, six male) who had never received corticosteroid treatment and in eight (four female, four male) healthy control subjects. There was a tendency toward an increase in aromatase activity in SLE patients when compared to control subjects. Among SLE patients the aromatase activity varied inversely with disease activity. Patients with SLE had decreased androgen and increased estrogen levels. Aromatase activity in SLE patients had significant direct correlation with estrogen levels. These data suggest that abnormal regulation of aromatase activity may partially explain the abnormalities of estrogen synthesis in SLE.
Two Sisters Producing Anti-U1RNP Exhibit Serological Concordance and Clinical Discordance
Authors: Reichlin Morris , Abumohor Patricia , Itoh Yasuhiko
Published: November 2007

Two sisters had autoimmune responses to the U1RNP particle that were quantitatively similar and/or identical in molecular characteristics. No other autoantibodies were demonstrable. Both sisters immunoprecipitated only U1RNA, had a reaction of identity in gel diffusion, bound the 68-kDa band in HeLa cell extract in Western blot, and reacted almost equally to a rabbit anti-idiotypic reagent made against either sister's isolated anti-U1RNP Fab fragments. They both carried a DR4 allele, which has been associated with anti-U1RNP production in several studies. While the sisters both had Raynaud's phenomenon, their clinical pictures were otherwise dissimilar. One had a seizure disorder (Ju); the other had polymyositis and features of scleroderma (Je). In sister Ju, Raynaud's phenomenon was manifest for the first time in association with the appearance of precipitating anti-U 1RNP.
Monoclonal Gammopathy in Systemic Lupus Erythematosus
Authors: Porcel J.M. , Ordi J. , Tolosa C. , Selva A. , Castro-Salomo A. , Vilardell M.
Published: November 2007

In order to ascertain the incidence of monoclonal gammopathy (MG) in systemic lupus erythematosus (SLE), 120 SLE patients were evaluated. Four patients (3.3%), two of whom were under 50 years of age, were found to have a monoclonal immunoglobulin in their serum. Our data agree with the previous literature in demonstrating a higher incidence of MG in SLE patients in comparison with the general population. Neither the clinical importance nor the pathogenetic significance of this association is known.
Refractory Nephrotic Syndrome in Lupus Nephritis: Favorable Response to Indomethacin Therapy
Authors: Espinoza Luis R. , Jara Luis J. , Martinez-Osuna Pindaro , Silveira Luis H. , Cuellar Marta Lucia , Seleznick Mitchel
Published: November 2007

The effects of indomethacin on urinary protein excretion, levels of serum albumin and renal function were studied prospectively in six patients with systemic lupus erythematosus (SLE) and refractory nephrotic syndrome due to lupus nephritis. Two had membranoproliferative glomerulonephritis, two had diffuse proliferative glomerulonephritis, and one each had mesangioproliferative and membranous glomerulonephritis. All experienced a considerable reduction in urinary protein excretion and an increase in serum albumin. Indomethacin was discontinued in two patients because of side effects, and proteinuria recurred to pretreatment levels. The decrease of proteinuria continued during long-term treatment in three patients. Indomethacin did not cause a permanent decline in renal function. Our results suggest that therapy with indomethacin may be beneficial for the treatment of refractory nephrotic syndrome in selected SLE patients. However, because of potential side effects the administration of indomethacin should be monitored closely.
HLA Antigens and Complement C4 Allotypes in Patients with Chronic Biologically False Positive (CBFP) Seroreactions for Syphilis: A Follow-Up Study of SLE Patients and CBFP Reactors
Authors: Stephansson E.A. , Koskimies S. , Lokki M.-L.
Published: November 2007

We report a follow-up of our previous study of HLA markers in 118 unrelated patients: 49 with definite systemic lupus erythematosus (SLE) (group 1), 32 with definite or probable SLE and chronic biologically false positive (CBFP) seroreactions for syphilis (group 2), and 37 CBFP reactors (group 3). Definite SLE was confirmed in 28 (90.3%) of the patients in group 2, equally in HLA B8- and HLA B7-positive patients. Three of the CBFP reactors developed SLE, two (40%) out of five HLA B8-positive as compared to one (6.6%) out of 15 HLA By-positive CBFP reactors (P = 0.07). Fourteen patients died (groups 1 and 2). Eight of the 24 HLA B8-positive patients died in contrast to one of the 20 HLA B7-positive patients (P < 0.02).

Of the CBFP reactors, 70.9% had complement C4 null alleles as compared to 47.9% in controls (P = 0.05) and 50% had C4A null alleles as compared to 17.8% in controls (P < 0.05). C4B null alleles were found in 28.6% (28.6% in controls, P is not significant). The null alleles for C4A were not solely in a linkage disequilibrium with the HLA B8 DR3 haplotype. CBFP reactors with C4A null alleles had a higher risk of developing SLE, lupus-like disease or symptoms such as photosensitivity, cutaneous vasculitis and/or autoantibodies than did those with no C4A null alleles (P < 0.02).
Immune Ablation with Stem-Cell Rescue: A Possible Cure for Systemic Lupus Erythematosus?
Authors: Marmont Alberto M.
Published: November 2007

The impressive prolongation of survival has been the most important progress made in clinical systemic lupus erythematosus (SLE). Quality of life has also greatly improved, including pregnancy. However, persisting disease and therapy-related morbidity outcomes justify new approaches, different from the usual long-term palliative immunosuppression. Haematopoietic stem cells (HSCs) from healthy histocompatible mice are capable of curing murine SLE after eradication of the original HSCs with total body irradiation. Syngeneic and even autologous HSCs are also capable of curing induced experimental autoimmune diseases such as adjuvant arthritis and experimental allergic encephalomyelitis. In man allogeneic bone-marrow transplantation (BMT) is becoming progressively safer, but cannot yet be offered to SLE patients. However, syngeneic transplants from twins non-concordant for the disease would be justified.

Conditioning with high-dose cyclophosphamide followed by autologous HSC rescue, from the marrow and/or from the peripheral blood, may already be regarded as a powerful immunosuppressive procedure for selected cases of SLE and other severe autoimmune diseases. Autologous transplant procedures are not saddled with the immunologic problems of allo-BMT. Although eradication of SLE may not be achieved by auto-BMT, minimal residual immunologic disease can be suppressed or controlled, and long-term self-maintained remissions may be expected.
Factitious Systemic Lupus Erythematosus
Authors: Fonseca Eduardo , Rubio Gabriel
Published: November 2007

We report the case of a 15-year-old girl who simulated a complex clinical picture including cutaneous lesions, fever, arthralgia, asthenia and oliguria. A diagnosis of probable systemic lupus erythematosus (SLE) was assumed by numerous specialists and steroid therapy instituted. Factitious SLE should be considered for differential diagnosis of SLE, especially when laboratory evidence for autoimmunity is not demonstrated.
Parkinson-Like Symptoms as a Manifestation of Systemic Lupus Erythematosus
Authors: Miyoshi Yoshinori , Atsumi Tatsuya , Kitagawa Hirohiko , Ogura Nobutaka , Amasaki Yoshiharu , Tsutsumi Akito , Ohnishi Katsunori , Fujisaku Atsushi , Sagawa Akira , Koike Takao
Published: November 2007

A 42-year-old Japanese woman with systemic lupus erythematosus (SLE) developed Parkinsonian-like movements. Steroid pulse therapy was most effective and additional anti-Parkinsonian drugs were not required. Although psychosis, seizures and meningitis are common central nervous system (CNS) manifestations in SLE patients, Parkinsonian-like symptoms are extremely rare. The putative genesis and treatment of CNS lupus are discussed.
Reflex Seizures as Initial Manifestations of Systémic Lupus Erythematosus in Childhood
Authors: Brinciotti Mario , Ferrucci Giovanna , Trasatti Giovanni , Priori Roberta , Squilloni Elisabetta , Valesini Guido
Published: November 2007

We report a 10-year-old girl with reflex seizures characterized by visual and acoustic hallucinations, induced by visual and acoustic stimulations. The EEG showed atypical spike-wave discharges on the left temporo-occipital area, markedly activated by visual and acoustic stimuli (intermittent light, pattern-reversal stimulation and monoaural right pure tone). The patient was treated with carbamazepine and seizure stopped within 7 months. After 10 months from the start of the therapy she developed signs of systemic lupus erythematosus.
In Vitro Modulation of Anti-DNA Secreting Peripheral Blood Mononuclear Cells of Lupus Patients by Anti-Idiotypic Antibody of Pooled Human Intravenous Immune Globulin
Authors: Evans Marilyn , Abdou Nabih I.
Published: November 2007

Anti-idiotypic antibody and its F(ab')2 fragments prepared from pooled normal human IgG had a partial inhibitory effect on the spontaneous in vitro secretion of anti-DNA antibodies from blood mononuclear cells of lupus patients. The inhibitory effect was specific for anti-DNA secretion as the anti-idiotype failed to inhibit the spontaneous secretion of anti-tetanus toxoid in the same culture supernatants. Non-anti-DNA IgG or its F(ab')2 fragments from pooled normal human IgG had less inhibitory effect on anti-DNA secretion than the purifieed anti-Id. In vitro polyclonal IgG secretion by lupus blood mononuclear cells was equally inhibited by both the anti-idiotype and the non-anti-DNA IgG of pooled normal human IgG. There was no correlation between the in vitro suppression of anti-DNA and that of total IgG or of anti-tetanus toxoid antibody. Pooled normal human IgG could have a potential beneficial effect in the therapy of systemic lupus erythematosus by inhibiting anti-DNA production via an anti-idiotypic mechanism.
Recurrent Annular Erythema Anti-SSA/Ro and Anti-SSB/La Antibodies Localized on Palms and Fingers an Elderly Man
Authors: Satoh Minoru , Ajmani Ajay K. , Yamagata Hajime , Okubo Kenji , Akizuki Masashi
Published: November 2007

A 69-year-old Japanese man with recurrent annular erythema localized on palms and flexor surface of fingers with anti-SSA/Ro and anti-SSB/La antibodies, is reported. The present case indicates that even in an elderly man with atypical localization, annular erythema with autoimmunity may be considered and serological analysis should be performed. Systematic studies will be required to understand the relationship between 'recurrent annular erythema associated with anti-SSB/La antibodies' in Japanese, subacute cutaneous lupus erythematosus (SCLE) and 'annular erythema associated with Sjogren's syndrome'.
Review: Anti-Endothelial Cell Antibodies: a Need for Standardization
Authors: Adler Yehuda , Salozhin Konstantin , Le Tonqueze Michelle , Shoenfeld Yehuda , Youinou Pierre
Published: November 2007

Twenty years have passed since the original description of the anti-endothelial cell antibodies (AECA). It is widely acknowledged that the presence of circulating autoantibodies against endothelial cells surface antigens, found in a number of patients with connective tissue disease and vasculitis, is one of the driving mechanisms for the observed vascular injury and might be an important factor in initiating the pathogenesis of vascular abnormalities. AECA data regarding the prevalence, technical problems, presence with other autoantibodies, antigen distribution and immune endothelial cell injury associated with these autoantibodies, requires standardization for determining the precise pathophysiologic and immunologic role of anti-endothelial cell antibodies.
A Controlled Trial of Pulse Cydophosphamide Versus Pulse Methylprednisolone in Severe Lupus Nephritis
Authors: Sesso Ricardo , Monteiro Marcia , Sato Emilia , Kirsztajn Gianna , Silva Liana , Ajzen Horacio
Published: November 2007

We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m 2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis.
Anti-Interleukin-6 and Soluble Interleukin-6 Receptor in Systemic Lupus Erythematosus
Authors: Evans Marilyn , Abdou Nabih I.
Published: November 2007

IL-6, soluble IL-6 receptor and IgG with anti-IL-6 activity were measured in the plasma of 14 lupus patients and 10 normal subjects. The capacity of peripheral blood mononuclear cells to spontaneously produce IL-6 in vitro was also measured. Our results indicate that IL-6 plasma levels in patient plasma as measured by ELISA were not different from normal but that supernatant levels were significantly lower than normal (P < 0.05). In vitro IgG production was comparable for all lupus patients' cells irrespective of the in vitro IL-6 levels. Plasma soluble IL-6 receptor levels directly correlated with IL-6 production capacity of SLE cells and the ratio of soluble receptor to anti-IL-6 directly correlated with IL-6 production in patients but not in normals. Inhibition assays demonstrated competition between anti-IL-6 and soluble receptors for IL-6 and the inhibition by plasma of IL-6 binding to monoclonal anti-IL-6. We believe the interaction of anti-IL-6 and IL-6 receptor with IL-6 may contribute to the homeostasis in IL-6 activity in vivo and skewing of the soluble receptor/anti-IL-6 ration may contribute to the lupus disease process.
Antiphospholipid Antibody: Future Developments
Authors: Lockshin Michael D.
Published: November 2007

In September 1991, an NIH workshop on molecular and biological aspects of antiphospholipid antibodies (aPL) identified questions for future studies: are the antibodies defined by the ELISA and by the lupus anticoagulant tests the same? Is aPL directly responsible for disease? What is the antigen? What drives the production of aPL? What is the role of β2-glycoprotein I? What accounts for patient heterogeneity? Can a satisfactory animal model be developed? The NIH workshop did not address important clinical questions, including those of pathogenesis and treatment.

In 1994 many of these questions have at least partial answers. β2-glycoprotein I appears to be an obligatory component of the antigen, abnonnal coagulation is the probable central pathogenic event and animal models now exist. There are still critical unknowns that define a future research agenda: the genetics of the aPL syndrome, the relationship of aPL to SLE and mechanisms of pathogenesis (including why clotting is episodic and what is the cellular or anatomical location of the initial injury). Despite a decade of clinical studies, risk prediction for defined patient groups is only now beginning to be studied. There are still almost no randomized, prospective, controlled treatment trials on any aspect of the syndrome nor are there definitive answers regarding which among antiplatelet, anticoagulant or antithrombin therapies is superior, what is the role of immunosuppressive therapy and what experimental therapies might be introduced.

The molecular biology of the antigen-antibody interaction will soon be fully understood, then the cellular and the organism biology. Definitive treatment interventions may await this understanding but adequate therapies are available at this time to conduct important and effective prospective clinical trials.
Role of Genetic Factors in Drug-Related Autoimmunity
Authors: Adams Louis E. , Mongey Anne-Barbara
Published: November 2007

Although there is evidence to suggest that genetic factors play a major role in the pathogenesis of many of the rheumatic diseases, far less is known of their role in the induction and expression of human autoimmunity resulting from long-term exposure to drugs, chemicals and environmental agents.

Pharmacogenetic factors represent an important source of interindividual variation in response to drugs; most research to date has focused on genetic polymorphism of drug metabolism via N-acetylation, S-methylation or cytochrome P-450-catalyzed oxidation.

In drug-related autoimmunity, there is limited evidence that the host's genetic background plays a major role beyond the expression of autoantibodies.

More recent prospective studies have concentrated on the association of MHC-genes in the expression of autoimmunity and the susceptibility of patients to develop drug-related clinical syndromes.
Autoimmunity and Heavy Metals
Authors: Bigazzi Pierluigi E.
Published: November 2007

This brief review is focused on those heavy metals (cadmium, gold and mercury) that have strong associations with autoimmunity. Cadmium treatment of rats and mice results in autoimmune responses that vary with species and inbred strain of animals. However, there is no solid evidence demonstrating that the renal pathology observed in humans exposed to cadmium has an autoimmune pathogenesis. More clear-cut are the autoimmune effects of preparations containing gold salts, that have been widely used in the treatment of rheumatoid arthritis. Gold may cause autoimmune thrombocytopenia, immune complex-mediated glomerulonephritis and other autoimmune disorders. Similarly, there is solid evidence that mercury can induce autoimmune disease both in humans and experimental animals. The lessons to be derived from metal-induced autoimmunity relate to structure-activity relationship, pathogenesis, etiology and genetics. They probably apply to xenobiotic-induced autoimmune disease in general.
Anticardiolipin Antibodies in Infections are Heterogenous in Their Dependency on β 2-Glycoprotein I: Analysis of Anticardiolipin Antibodies in Leprosy
Authors: Hojnik Maja , Gilburd Boris , Ziporen Lea , Blank Miri , Tomer Yaron , Scheinberg Morton A. , Tincani Angela , Rozman Blaz , Shoenfeld Yehuda
Published: November 2007

We studied the effect of β 2-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine β2-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without β2-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of β2-GPI on the leprosy and APS sera binding to CL was confirmed using purified human β 2-GPI. Enhanced binding was seen if β2-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against β2-GPI were found by ELISA. Leprosy anti-β2-GPI antibodies appear to be a separate antibody population recognizing only β2-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their β 2-GPI requirement for binding to CL.
Hypergammaglobulinemic purpura of Waldenstrom associated with systemic lupus erythematosus: report of a case and review of the literature
Authors: Habib George S , Stimmer Mary M , Quismorio Francisco P
Published: November 2007

A patient with hyperglobulinemic purpura of Waldenstrom and systemic lupus erythematosus is reported. The coexistence of these two conditions which share a number of common clinical and laboratory features is rare. Treatment of the patient with prednisone, colchicine and hydroxy chloroquine led to the improvement of the cutaneous vasculitis and a drop in ESR, serum gamma globulins and IgM and IgG rheumatoid factors. The features of nine other cases and the immunopathogenesis of the disease are reviewed.
Appearance of systemic lupus erythematosus after thymectomy: four case reports and review of the literature
Authors: Mevorach Dror , Perrot Serge , Buchanan Neil MM , Khamashta Munther , Laoussadi Sadek , Hughes Graham RV , Menkes Charles Joel
Published: November 2007

The appearance of systemic lupus erythematosus (SLE) after thymectomy (or thymomectomy) is presented in four patients together with a comparative review of additional reports found in a Medline search for the years 1966-94 in the English and French literature.

Fourteen women and two men of average age of 39 years (range 11-66 years) at presentation, developed SLE after thymectomy (11 patients) or thymomectomy (five patients). Half developed SLE within 3 years after surgery (range 3 months to 18 years). The most common SLE manifestation was polyarthritis occurring in 15 of 16 patients either at presentation or during the first year. Other frequent manifestations included skin rashes, fever, cytopenias and pleuritis. Two rare manifesta tions of SLE, optic neuritis and transverse myelitis, were reported in two patients. Thymic hormone activity was measured in one patient and was undetectable compared with normal controls. HLA studies in eight patients showed the combination of A1, B8 in four.

In conclusion, the appearance of SLE after thymectomy or thymomectomy appears to be more than a coincidence. It may provide insights into the pathogenesis of SLE.
Prognostic determinants in lupus nephritis: a long-term clinicopathologic study
Authors: Donadio JV , Hart GM , Bergstralh EJ , Holley KE
Published: November 2007

Over the past 50 years, survival has improved in patients with systemic lupus erythematosus and associated nephritis. Yet, there are few long-term outcome studies in patients with well-defined nephropathy. We examinbed the outcome of 439 patients with lupus nephritis who were seen at the Mayo Clinic between 1964 and 1986 in whom renal biopsies were assessed using the World Health Organization (WHO) classification. There were 341 women and 98 men (mean ± s.d., age 33.5 ± 14 years); 200 (46%) patients were hypertensive and 249 (57%) had impaired renal function at renal biopsy. All WHO morphologic classes were represented and 339 (77%) patients had class III, IV and V (the more severe forms of nephritis). Follow-up averaged 10.2 years per patient. At last contact, 286 (65%) patients were alive and 153 (35%) were dead. Overall patient survival was 80%, 69% and 53% at 5, 10 and 20 years after biopsy that was significantly worse than expected survival (P < 0.001). Ten-year cumulative patient survival improved comparing earlier to more recent time spans: 64% in 231 patients seen during 1964-75; 76% in 2089 patients studied during 1976-86 (P = 0.03). Survival free of renal failure was 83%, 74% and 64% at 5, 10 and 20 years, and survival was unfavorably influenced by progressive WHO class, hypertension, impaired renal function, nephrotic range proteinuria, hypoalbuminemia and anemia. Multivariate analysis found impaired renal function, increased urine protein, anemia and younger age to be independent predictors of renal failure. WHO class was not a significant predictor when adjusted for these four factors. Cardiovascular events accounted for 48% of the known deaths and were equally distributed across all WHO classes, followed by infections, renal failure, malignancy, respiratory failure and gastrointestinal bleeding. Severe nephritis, nephrotic syndrome, hypertension and anemia remain strong predictors of a poor renal outcome. Prospective randomized studies stratifying for these factors are needed to find optimal immunosuppressive regimens to improve renal survival.
Association of anticardiolipin antibodies and abnormal nailfold capillaroscopy in patients with systemic lupus erythematosus
Authors: Bongard Olivier , Bounameaux Henri , Miescher Peter-Anton , De Moerloose Philippe
Published: November 2007

Anticardiolipin antibodies (aCL) are found in about 40-50% of patients suffering from systemic lupus erythematosus (SLE) and their presence carries an increased risk of thromboembolism. Since there is a high prevalence of nailfold capillary abnormalities in patients with SLE, we studied the relationship between aCL and skin microcirculatory changes or vascular symptoms in 51 consecutive patients with SLE (49 women, 2 men, 34.8 ± 13.7 years).

Twenty-two patients (43.1 %) had positive aCL (IgG 22 (5-60) GPL; IgM 5 (3-16.5) MPL; median titre and range) and 12 (54.5%) of them had abnormal capilloscopic findings. By contrast, among the 29 patients without aCL, only six (20.7%) had an abnormal capillaroscopy (P = 0.027). There was no correlation between either aCL or capillaroscopy and Raynaud's phenomenon.

These results show a relationship between aCL and nailfold capillary changes in patients with SLE, suggesting a direct damage of the vascular endothelium by aCL.
Skeletal muscle lymphocytic vasculitis in systemic lupus erythematosus: relation to disease activity
Authors: Lim KL , Lowe J. , Powell RJ
Published: November 2007

Lymphocytic vasculitis (LV) characterises systemic lupus erythematosus (SLE) and this potentially reversible lesion, which may be subclinical, may imply overt systemic disease activity. Needle quadriceps muscle biopsy was performed in 26 unselected patients with SLE and the presence of LV in these muscle specimens was compared with SLE disease activity scored using the British Isles Lupus Assessment Group Index (BILAG). Ten of the 22 patients with active disease showed evidence of LV compared with none of the four patients with inactive disease. In the patient group with LV, significantly higher ESR and urine neopterin values were found with P = 0.002 and P = 0.02, respectively compared with patients without LV. Features of vasculitis (as defined by BILAG) were also significantly more common in these patients (P = 0.005). None of the other parameters, including creatine kinase, were significantly different between the two patient subgroups. Thus, LV in needle quadriceps muscle biopsy specimens is a further valuable marker of disease activity in patients with SLE and might provide histological evidence of a systemic vasculitic process in a group of patients with diverse clinical manifestations.
Clinical manifestations of hepatic arteritis in systemic lupus erythematosus
Authors: Huang De-Feng , Yang An-Hung , Lin Bao-Cherng , Wang Soo-Ray
Published: November 2007

Hepatic arteritis is a rare complication in systemic lupus erythematosus (SLE). Information about its clinical manifestations is still very limited. Elevated serum r-glutamyl transpeptidase and alkaline phosphatase levels, but without elevated bilirubin and transaminase levels, were found in the present report to be the clinical presentation of hepatic arteritis. This clinical picture originally suggested a disease of the biliary tree. Hepatic arteritis must be included in the differential diagnosis of biliary tract disorders in SLE.
Role of β2-glycoprotein I in the antiphospholipid antibody binding to endothelial cells
Authors: Le Tonquèze M. , Salozhin K. , Dueymes M. , Piette J.-C. , Kovalev V. , Shoenfeld Y. , Nassonov E. , Youinou P.
Published: November 2007

A group of anticardiolipin antibodies (aCL) require β2-glycoprotein I (β2GPI) to recognize their target, which might be located on endothelial cells (EC) and/or platelets. Following incubation with epithelial cells, 13 of 30 lupus sera retained EC-reactive antibodies of the IgG, IgA and IgM isotypes. Associated aCL and anti-phosphatidylethanolamine antibodies were partly absorbed on eC as well as EC. The former antibodies were more efficiently removed in the presence than in the absence of the latter. The presence of β2GPI in the affinity-purified aCL preparations may explain their binding to EC, as this cross-reaction was abrogated by the removal of the cofactor and restored by its re-introduction. Seventy four per cent of EC were faintly stained with polyclonal or monoclonal antibody directed to the cofactor. The β 2GPI mediated aCL binding to EC membranes could thus be influential in the development of thrombosis and/or thrombocytopenia in aCL-positive patients.
Characterization of autoimmune thyroiditis in MRL-lpr/lpr mice
Authors: Green L.M. , LaBue M. , Lazarus J.P. , Colburn K.K.
Published: November 2007

MRL-lpr/lpr mice are genetically predisposed to develop a systemic lupus erythematosus-like syndrome that is clinically very similar to the human disease. The results presented here demonstrate, for the first time to our knowledge, that MRL-lpr/lpr mice also develop thyroiditis as part of their systemic autoimmune disorder. The thyroid gland was infiltrated by immunocomponent cells with defined lymphoid follicular centers and extensive interstitial lymphocytes dispersed throughout the thyroid epithelium. All the diseased mice were hypothyroid with reduced, relative levels of thyroid hormone (free T4) and elevated levels of thyroid-stimulating hormone (TSH). They also had high concentrations of circulating IgG class autoantibodies directed against thyroglobulin, thyroperoxidase and double-stranded DNA. The MRL-+/+ age-matched allelic counterpart mice had relatively few lymphocytes in their thyroid tissue, and normal levels of thyroxine and TSH. The non-diseased mice also had undetectable levels of thyroid reactive autoantibodies tested for by enzyme-linked immunosorbent assays. Collectively these findings document that the MRL-lpr/lpr mice spontaneously develop autoimmune thyroiditis and can be used as a model for the study of thyroid-specific autoimmunity.
Model for the neuromuscular complications of systemic lupus erythematosus
Authors: Brey R.L. , Cote S. , Barohn R. , Jackson C. , Crawley R. , Teale J.M.
Published: November 2007

The purpose of this study is to evaluate nerve and muscle physiology and histopathology in a murine lupus model. Muscle strength, compound muscle action potentials (distal latency and amplitude), proximal limb muscle, sciatic nerve and joint specimens were studied in MRL/lpr (lupus model) and MRL/++ (control) mice. MRL/lpr mice showed decreased muscle strength (P<10-6 Wilcoxon rank sum), lower compound muscle action potential mean amplitude and prolonged distal latency (P = 0.005 and 0.042, Mann-Whitney U-test), and muscle and nerve inflammation (P = 0.002 and P = 0.037, Fisher's exact test) compared with MRL/++ mice. The MRL/lpr strain evaluated in this study demonstrated muscle weakness, abnormal motor nerve conduction studies and inflammation of both muscle and nerve. These features make it an excellent model for studying the neuromuscular complications of lupus.
Portal hypertension associated with anticardiolipin antibodies in a case of systemic lupus erythematosus
Authors: Takahaski C. , Kumagai S. , Tsubata R. , Sorachi K.-I. , Ozaki S.-I. , Imura H. , Nakao K.
Published: November 2007

A 26-year-old man with systemic lupus erythematosus (SLE) and a history of acute myocardial infarction developed portal hypertension accompanied by abnormal liver function and esophageal varices. As his clinical course suggested the possibility of antiphospholipid syndrome, a titer of anticardiolipin antibody (aCL) was serially measured using an enzyme immunoassay with β2-glycoprotein I as a cofactor. The titer of aCL increased with the development of portal hypertension, and promptly decreased with the improvement of liver function just after corticosteroid therapy. The long-term course in this case suggests that aCL may cause portal hypertension associated with SLE.
Autoantibodies to topoisomerase I in a patient with systemic lupus erythematosus without features of scleroderma
Authors: Stojanov L. , Satoh M. , Dooley M.A. , Kuwana M. , Jennette J.C. , Reeves W.H.
Published: November 2007

We report a woman with systemic lupus erythematosus (SLE) with diffuse proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical manifestations consistent with SLE without clinical evidence of scleroderma. The reactivity of her serum autoantibodies with the phosphoproteins ribosomal P, topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes comprised in part of phosphate groups. This may explain the unexpected coexistence of marker autoantibodies for SLE and scleroderma, possibly with implications for the mechanisms of autoantibody generation.
Lack of association between the MHC linked OTF3 gene and systemic lupus erythematosus
Authors: Pablos JL , Carreira PE , Gomez-Reino JJ
Published: November 2007

The objective of this study was to investigate whether an octamer transcription factor gene ( OTF3) located within the MHC region of chromosome 6 is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. An OTF3 HindIII polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction amplified genomic DNA in 69 patients with SLE and 60 controls. No differences in the OTF3 allelic or genotypic distribution between healthy controls and patients with SLE were found. In the group of patients with diffuse proliferative glomerulonephritis, where we have previously detected the strongest MHC association, we did not observe OTF3 linkage either.

In conclusion, the OTF3 gene does not appear to be associated with SLE in the Spanish population. This might be due to the distance of the gene from the HLA class II-III region where more relevant autoimmune-related genes are located.
Reversal of thrombocytopenia following oral anticoagulation in two patients with primary antiphospholipid syndrome
Authors: Ames P.R.J. , Orefice G. , Brancaccio V.
Published: November 2007

We report on two patients with the primary antiphospholipid syndrome who had significant thrombocytopenia. In both patients platelet number improved soon after initiation of oral anticoagulation. Possible mechanisms for the resolution of thromboeytopenia are discussed.
Development of polyarteritis nodosa in the course of inactive systemic lupus erythematosus
Authors: Vivancos J. , Soler-Carrillo J. , Ara-del Rey J. , Font J.
Published: November 2007

A 63-year-old woman developed a clinical and pathological picture of polyarteritis nodosa (PAN). Systemic lupus erythematosus (SLE) had been diagnosed 12 years previously, and she had been symptom and therapy-free for a decade. Development of 'primary' systemic vasculitis in SLE patients has rarely been described previously and the significance of this association remains unclear. The possible explanation for this transition from one connective tissue disease to another is discussed.
The antiphospholipid syndrome and SLE: is there a clue in the link between complement and coagulation?
Authors: Merrill JT , Lahita RG
Published: November 2007

The heterogenous immunoglobulins known as antiphospholipid antibodies (APLA) or . lupus 'anticoagulants' (LA) are prevalent in lupus patients and have been implicated in life-threatening thromboembolic events1-3. Unfortunately, observing the presence of these antibodies in an individual does not predict the likelihood of an event nor does it predict when it may occur4-6. A pathogenic role for these antibodies is supported by the observ ation that high titers and IgG isotype confer an increased risk of thromboembolism7. Addi tionally, numerous reports indicate that isolated patient antibodies interfere with various elements of the coagulation cascade8-15. Nevertheless, attempts to correlate specific anti body characteristics with the future likelihood of a hypercoagulable event in an individual patient16 have been unsuccessful to date. Given such uncertainty combined with the poten tial complications of anticoagulant medications, patients are generally not treated until sig nificant morbidity has occurred. Finally, because of the apparent high rate of reoccurrence 17 most patients must remain on anticoagulant therapy indefinitely, regardless of need.
Fluctuations of antibody to ribosomal P proteins correlate with appearance and remission of nephritis in SLE
Authors: Martin AL , Reichlin M.
Published: November 2007

Antibodies to ribosomal P proteins are found in widely variable proportions (up to 42%) of patients with SLE depending on the ethnic background of the patient population. Neuropsychiatric disease was first recognized to have increased prevalence with anti-P and more recently liver and renal disease. We describe four patients with SLE and circumscribed episodes of nephritis of relatively short duration. In two patients, antibodies to ribosomal P protein were the only specificity detected at the time of appearance of active nephritis; and in the other two patients, the appearance and disappearance of anti-ribosomal P was simultaneously found with similar fluctuations in anti- dsDNA titers. Anti-ribosomal P antibodies were measured by Western blot and a P peptide-specific ELISA.

These data raise the possibility for a pathogenic role for anti-ribosomal P antibodies in lupus nephritis.