bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunosuppression follows systemic T lymphocyte activation in the burn patient
Authors: TEODORCZYK-INJEYAN J A , SPARKES B G , MILLS G B , PETERS W J 
Published: July 2010

SUMMARYA general consensus that thermal injury affects T lymphocyte function adversely is supported particularly by the observation that burned patients’ lymphocytes secrete reduced levels of biologically active IL-2 in vitro. In the same patients, however, high serum concentrations of the low-affinity IL-2 receptor (IL2Rα), a product of an IL-2-activated gene, have been observed. In this study a significant proportion of patients also demonstrated over-physiological levels (from 2 to 500 U/ml) of serum IL-2 ascertained by immunoassay. Increases in serum IL-2 content correlated significantly (P &lt; 002) with those of serum IL-2Rα during the first week post-burn. Later, serum IL-2Rα levels continued to increase up to 30 days while IL-2 eventually declined. Thus, augmented secretion of IL-2Rα appears related to the high serum IL-2 content. Therefore refractoriness to further immune stimulation may be due to early activation of the lymphoid system, rather than to an intrinsic incapacity of T lymphocytes for generating sequential responses.
Occurrence of lymphocytotoxins in multi-case rheumatoid arthritis families: relation to HLA
Authors: TANEJA V , MEHRA N K , SINGH R R , ANAND C , MALAVIYA A N 
Published: July 2010

SUMMARY
The presence of lymphocytotoxic antibodies (LCA) and their association with HLA haplotypes has been studied in 27 multi-case rheumatoid arthritis (RA) families (13 multiplex and 14 simplex) in Northern India. Of the total 59 RA patients, 69.4% had cytotoxins in their sera as compared with 2.5% of healthy controls. No differences were observed in the frequency of LCA in relation to sex and rheumatoid factor. LCA against B cells were significantly more predominant than those against T cells. Twenty families studied for correlation of HLA with LCA showed greater intensity of reaction with DR4+ haplotypes, particularly in simplex families. Similarly, the frequency of LCA among patients and unaffected parents was greater in simplex compared with multiplex families. Haplotype sharing with the patient was increased in the relatives positive for cytotoxins in these families. An immunogenetic contribution made by the affected parent and B common environmental stimulus may be responsible for the increased production of LCA in multi-case families with RA.
Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis
Authors: SAVIGE J A , GALLICCHIO M C , STOCKMAN A , CUNNINGHAM T J , ROWLEY M J , GEORGIOU T , DAVIES D 
Published: July 2010

SUMMARYAnti-neutrophil cytoplasm antibodies (ANCA) occur occasionally in rheumatoid arthritis (RA), but their incidence and clinical significance have been unclear. In this study we have investigated 58 patients with RA. In 22 patients the disease was inactive and the remaining 36 with active disease were further subdivided into those without clinical evidence of vasculitis (26), those with cutaneous vasculitis (8) and those with systemic vasculitis (2). ANCA were demonstrated by indirect immunofluorescence in 10 of the 58 patients (17%), While both pcrinuclear (pANCA) and cytoplasmic (cANCA) staining were detected, pANCA were more common (70%). Neutrophil-specific anti-nuclear antibodies (ANNA) were demonstrated in a further eight sera (14%) and ANA were detected on Hep-2 cells in 30 of the 58 sera (52%). ELISAs for the detection of anti-myeloperoxidase and anti-elastase antibodies were then established. Five sera with pANCA and five that contained ANNA were negative for both anti-myeloperoxidase and anti-elastase antibodies, suggesting other as yet unidentified cytoplasmic antigens as the target molecules. However, anti-myeloperoxidase or anti-elastase antibodies were found in four sera that had homogeneous or speckled ANA on both Hep-2 cells and neutrophils. One serum contained both antibodies. The presence of ANCA detected by indirect immunofluorescence or of anti-myeloperoxidase or anti-elastase antibodies in these patients with RA was not associated with disease activity nor with the demonstration of cutaneous vasculitis or renal disease (P NS). A possible association with systemic vasculitis remains to be confirmed. There is an incomplete correlation between indirect immunofluorescence patterns and antibody specificity in ELISA systems.
Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus
Authors: ICHIKAWA T , TAGUCH O , TAKAHASHI T , IKEDA H , TAKEUCHI M , TANAKA T , USUI M- , NISHIZUKA Y 
Published: July 2010

SUMMARYThis paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus. The uveoretinitis was characterized histologically by progressive loss of the pholoreceptor layer, observed in 4.0, 17.6, 42.9% and 71.4 % of such mice at 3, 5, 7 and 12 months of age. respectively. Mice with uveoretinitis were shown to huve serum IgG antibody reactive by indirect immunofluorescence with retinal photo receptors, and with interphotoreceptor retinoid-binding protein (IRBP). but not retinal S-antigen. by immunoblotting and ELISA. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4* T cells from diseased animals. This is the first experimental model of a (T cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.
New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response
Authors: ATANASSOV C , BRIAND J-P , BONNIER D , VAN REGENMORTEL M H V , MULLER S 
Published: July 2010

SUMMARYThe antibody response of rabbits immunized with a total histone mixture containing randomly coiled H1/H5, H2A, H2B, H3 and H4 devoid of DNA was investigated in direct and competitive ELISA. The antisera were tested with isolated histones and chromatin and with a series of overlapping synthetic peptides covering the entire sequences of the four core histones and two peptides of H I. It was found that the New Zealand (NZ) white rabbits immunized with the total histone (TH) mixture complexed with RNA produced IgG antibodies reacting with histones and with a number of histone peptides but not with chromatin. The antisera also contained IgG antibodies which bound components that correspond lo common target antigens in autoimmune diseases such as native dsDNA, peptides of Sm-D antigen, ubiquilin, branched peptides of ubiquitinated H2A and poly(ADP-ribose). By competition experiments, it was shown that these antibodies corresponded to non-crossreacting antibody populations. New Zealand rabbits immunized with TH in the absence of RNA or random outbred rabbits immunized with the RNA-complexed histone fraction produced antibodies reacting with histone, chromatin and very few histone peptides. while no activity with non-related antigens was observed. The pattern of reactivity of antisera raised in NZ rabbits with RNA-complexed TH was found lo be very similar to that observed in sera of patients with systemic lupus erythematosus while, in contrast, the antibody response was very different in NZ or outbred rabbits immunized with various native nuclear particles and with individual histones. Altered nucleosome particles rather than native nucleosomes may represent the antigenic stimulus giving rise to autoantibodies.
Serum soluble CD4 and CD8 levels in Kawasaki disease
Authors: FURUKAWA S , MATSUBARA T , TSUJI K , MOTOHASHI T , OKUMURA K , YABUTA K 
Published: July 2010

SUMMARYThe levels of soluble CD4 (sCD4) and sCD8 in serum correlate with the T cell subset activation and may be important in monitoring and characterizing disease processes during immunological diseases. We compared acute Kawasaki disease (KD) with anaphylactoid purpura (AP) and acute febrile viral infections, such as measles and infectious mononucleosis (IM), in terms of serum sCD4 and sCD8 levels. The levels of serum sCD4 and sCD8 were measured by a sandwich enzyme immunoassay. In addition, peripheral blood mononuclear cell subsets were analysed by single and two-colour flow-cytometric analyses in KD and IM patients. The levels of serum sCD4 and sCD8 were significantly elevated in patients during acute stages of KD, measles and IM, but not AP. Peripheral blood CD4+, CD8+ and also HLA-DR+ T cells count did not increase during the acute stage of KD; however, peripheral blood CD8+ and HLA-DR+ T cell counts were increased during the acute stage of IM. Our results suggest that there is a low level of activation of peripheral blood T cells during acute KD, or that infiltrated T cells in some local tissues of KD patients contribute to the elevated levels of serum sCD4 and sCD8.
Urinary IL-6: a marker for mesangial proliferative glomerulonephritis?
Authors: GORDON C , RICHARDS N , HOWIE A J , RICHARDSON K , MICHAEL J , ADU D , EMERY P 
Published: July 2010

SUMMARYA prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage.
Differentiation between vascular permeability factor and IL-2 in lymphocyte supernatants from patients with minimal-change nephrotic syndrome
Authors: HESLAN J-M J , BRANELLEC A I , PILATTE Y , LANG P , LAGRUE G 
Published: July 2010

SUMMARYImmunolherapy of cancers with recombinant IL-2 induces a vascular leak syndrome which is mainly due to an increase in vascular permeability. A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS) and appeared very similar to IL-2. Here we have undertaken a further characterization of VPF in order to determine how closely related this factor was to human IL-2. Both the IL-2 bioassay and Western blot analysis of the MCNS lymphocyte concentrated supernatants with high VPF activity revealed the presence of low quantities of IL-2. Preparative isoelectrofocusing (IEF)orconcentratedsupernatanls resolved each lymphokine in a separate peak, with apparent pIs of 5.2 for VPF and 7.5–10. for IL-2. Since a sensitive IL-2 ELISA failed to exhibit any significant antigenic presence of IL-2 in the IEF fractions with the highest VPF activity, we conclude that VPF activity of the concentrated supernatanis is not related to IL-2 nor to a biologically inactive form of IL-2. When concentrated supernatants were subjected to preparative SDS-PAGE, VPF activity was recovered within low mol. wt material (1–12 kD). Immuno-adsorption experiments gave definite proof since the complete removal of IL-2 from concentrated supernatants did not affect the VPF activity. Although high amounts of IL-2 increased vascular permeability, our experiments clearly demonstrate that VPF is a lymphokine distinct from IL-2.
The H3 anti-phospholipid idiotype is found in patients with systemic lupus erythematosus (SLE) but not in patients with syphilis
Authors: HOHMANN A , COMACCHIO R , BOSWARVA V , SUTJITA M , BRADLEY J 
Published: July 2010

SUMMARYThe human H3 idiotype. defined by a mouse monoclonal antibody S2.9, is commonly found in patients with SLE where it is correlated with the amount of anti-cardiolipin antibodies. No correlation between the amount of anti-cardiolipin antibody and the H3 idiotype is found in patients with syphilis. Using the S2.9 antibody, serum from each of 10 patients with SLE and eight patients with syphilis was separated into H3-bearing and H3-negative fractions. Comparison of the partition of anti-cardiolipin antibody in these two groups of patients revealed that much of the anti-cardiolipin antibody (44–91%) was found in the H3+ fraction in patients with SLE; in patients with syphilis. virtually none of the anti-cardiolipin antibody was H3+. In patients with SLE. the H3+ fraction contained both IgG and IgM and antibodies of both kappa and lambda light chains. The H3+ fraction was polyspecific and frequently reacted with dsDNA.
Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-γ)
Authors: AULITZKY W E , GROSSE-WILDE H , WESTHOFF U , TILG H , AULITZKY W , GASTL G , HEROLD M , HUBER C 
Published: July 2010

SUMMARYIn order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-γ (rIFN-γ) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 μg rIFN-γ three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN-γ. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 μg rIFN-γ. The increments peaked after 2–4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rlFN-γ. The correlation observed between induction of beta-2-microglobulin and soluble HLA class 1 proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies.
Lactate dehydrogenase (LDH) isoenzymes and proliferative activity of lymphoid cells—an immunocytochemical study
Authors: PAN L , BEVERLEY P C L , ISAACSON P G 
Published: July 2010

SUMMARYIn a recent immunohistochemical study, we suggested that elevation of LDH isoenzymes is generally related to cell proliferalion. To explore this relationship further, we have now examined the expression of H- and M-type LDH isoenzymes immunocytochemically in human resting and mitogen-activated B and T lymphocytes. In the resting state, T lymphocytes showed strong staining for H-type LDH but showed little or no staining for M-type LDH, while B lymphocytes showed only weak staining for M-type LDH. During activation of T cells, M-type LDH started to increase when cells entered the early stages of the cell cycle. The staining intensity increased to a maximum when the percentage of the T cells at the S/G2/M phases of the cell cycle reached its peak. M-type LDH expression declined when the activated T cells returned to their resting state. Staining for H-type LDH remained strong in T cells during activation. In B lymphocytes, both H- and M-type LDH isoenzymes increased concomitantly following activation and the staining intensity also correlated well with the percentage of the S/G2/M fraction. The expression of H- and M-type LDH was also determined in fresh leukaemia and a variety of lymphoid cell lines. It was noted that cells of chronic lymphocytic leukaemia (CLL) and pro-lymphocytic leukaemia (PLL), morphologically similar to normal lymphocytes, showed a LDH staining pattern resembling that of resting B lymphocytes, while lymphoblasts in T cell acute lymphoblastic leukaemia (T-ALL). high grade B cell lymphoma and Epstein Barr virus (EBV) transformed cell lines showed a LDH staining pattern similar to that in activated T or B lymphocytes. Taken together, our results have demonstrated a significant correlation between expression of LDH and proliferative activity of cells. Immunostaining with the MoAbs to H- and M-type LDH can, therefore, provide a useful means not only for identification of T and B lymphocytes but also for rapid evaluation of the proliferating fraction of normal and neoplastic human cell populations.
Raised serum levels of CD8, CD25 andβ2-microglobulin in common variable immunodeficiency
Authors: NORTH M E , SPICKETT G P , WEBSTER A D B , FARRANT J 
Published: July 2010

SUMMARYSoluble CD8, soluble CD4, soluble CD25 (IL-2 receptor), β2-microglobulin and the cytokine tumour necrosis factor-alpha (TNF-α) were measured in sera from patients with common variable immunodeficiency (CVI). Levels of soluble CD8, soluble CD25 and β2-microglobulin but not of soluble CD4 and TNF-α were raised significantly above levels in normal sera. Sera from patients with X-linked agammaglobulinaemia, who are also antibody deficient, did not show this marked elevation. The raised levels of soluble CD8, soluble CD25 and β2-microglobulin in CVI, correlated with the extent of the defects in the B lymphocytes assessed in vitro, as well as with the clinical severity of the disease. The selective release of these molecules into sera may indicate that abnormal cellular activation occurs in most CVI patients. It is also possible that the raised levels of these soluble molecules play a part in the immunodeficiency.
T cell response to purified filtrate antigen 85 fromMycobacterium bovisBacilli Calmette-Guerin (BCG) in leprosy patients
Authors: LAUNOIS P , HUYGEN K , DE BRUYN J , N’DIAYE M , DIOUF B , SARTHOUJ L , GRIMAUD J , Millan J 
Published: July 2010

SUMMARYT cell proliferation and IFN-γ production of peripheral blood mononuclear cells from 25 healthy controls and 39 leprosy patients were tested against BCG-bacilli and culture filtrate, Mycobacterium leprae and purified antigen 85 (the major secreted 30–32 kD protein antigen) from M. bovis strain BCG. In lepromin negative healthy controls, blastogenesis was low to M. leprae and completely negative to antigen 85. IFN-γ levels were very low, close to detection limits. In all lepromin positive controls, significant proliferation and IFN-γ secretion was found in response to M. leprae and antigen 85. In the group of lepromatous leprosy (LL) patients, 25/29 of patients (with either positive (13) or negative (12) lymphoproliferative response to BCG) were unreactive to M. leprae or to antigen 85. Four LL patients with positive T cell response to BCG responded with detectable lymphoproliferative response and IFN-γ secretion to antigen 85. All tuberculoid (TT) leprosy patients responded to BCG, M. teprae and antigen 85. Hence, T cells from leprosy patients and controls demonstrate a marked parallelism of responsiveness towards whole M. leprae and purified antigen 85 from M. bovis BCG, suggesting strong eross-reactivity between the two species and underlining the biological importance of such secreted antigens.
Suppressive effect of hyperbaric oxygenation on immune responses of normal and autoimmune mice
Authors: SAITO K , TANAKA Y , OTA T , ETO S , YAMASHITA U 
Published: July 2010

SUMMARYWe studied the effect of hyperbaric oxygenation (HBO) on immune responses in normal and autoimmune mice. Mice were exposed to HBO in an animal chamber at a pressure of 252.5 kPa for 1 h and once a day for 5 days. The immunization of C3H/He mice with sheep erythrocytes induced marked anti-sheep erythrocyte antibody response on day 7. However, this response was markedly suppressed in HBO-treated mice. The suppression is dependent on the duration of HBO and it works on the early and the late stage of antibody responses. HBO suppresses the development of both sheep erythrocyte-specific B cells and helper T cells after the immunization. Then, we tried to expose autoimmune mice to HBO. Spontaneous immunoglobulin production of NZB and MRL/Ipr spleen cells was also significantly suppressed by HBO. Furthermore, long term HBO exposure results in the suppression of the development of autoimmune symptoms such as proteinuria, facial erythema and lymphadenopathy in MRL/lpr mice. All these results suggest that HBO is applicable for the treatment of autoimmune diseases.
The effect of antibody isotype and antigenic epitope density on the complement-fixing activity of immune complexes: a systematic study using chimaeric anti-NIP antibodies with human Fc regions
Authors: VALIM Y M LUCISANO , LACHMANN P J 
Published: July 2010

SUMMARYA systematic study has been carried out to investigate the role of immunoglobulin isotype, epitope density, and antigen/antibody ratio on the capacity of immune complexes to activate the classical and alternative pathways of human complement and for the complexes subsequently to bind to erythrocyte C3b-C4b receptors (CR1). For this purpose, a series of chimaeric monoclonal anti-NIP antibodies was used, which all shared the same combining site but had different human constant domains. Antigen epitope density was varied by coupling different numbers of NIP hapten molecules to bovine serum albumin. All three parameters affect complement fixation. In general, complement activation is better in antibody excess and at equivalence than it is in antigen excess, and better at high epitope density than at low epitope density, although the effects are variable for different immunoglobulin isotypes and for the two pathways. It has been confirmed that IgG1 and IgG3 are good activators of the classical pathway and are tolerant to variations in both epitope density and antigen/antibody ratio. IgG4 and IgA do not activate the classical pathway in any circumstances. IgG2 activates the classical pathway only at high epitope density and at equivalence or antibody excess. IgM activates the classical pathway well only at the higher epitope densities and at equivalence or antibody excess but, in addition, shows an interesting and unexpected prozone phenomenon where immune complex in antibody excess inhibits complement activation by the classical pathway. The results of the alternative pathway activation are strikingly different. IgA is by far the best activator of the alternative pathway and is relatively tolerant to epitope density and to antigen/antibody ratio. IgM, IgG1 and IgG3 do not significantly activate the alternative pathway in any circumstances. IgG2 is the best IgG subclass for alternative pathway activation but requires high epitope density and equivalence or antibody excess. Binding to CR1 in general parallels the amount of complement fixed independent to the pathway by which it is fixed. However, IgG1 and IgG3 complexes in antigen excess activate complement well but bind poorly to CR1. Nascently formed complexes seem to bind complement in a way that is similar to that bound by preformed complexes, but are then less able to bind to red cell CR1. These observations help to explain the pathogenesis of complement activation in various autoimmune and immune complex diseases such as systemic lupus erythematosus, autoimmune thyroiditis and others.