New Role of Antiphospholipid Antibodies (APLA)? Correlations with Disease Activity in Non-Thrombotic and Thrombotic Autoimmune and Hematologic Disorders.
Authors: Horstman Lawrence L. , Bidot Carlos J. , Jy Wenche , Fontana Vincenzo , Duckiewicz Pamela , Ahn Eugene R. , Jimenez Joaquin J. , Ahn Yeon S. 
Published: October 2019

BACKGROUND. Although APLA are a known risk factor for thrombosis, clear understanding of this association remains elusive. In recent years our laboratory has conducted surveys of APLA by ELISA of several immune, inflammatory and other disorders, here compared.

METHODS. IgG and IgM to six target antigens (B2GP1, FVII, CL, PE, PS, PC) were measured. In most cases, platelet activation (by CD62P), endothelial activation (by endothelial microparticles, EMP) and lupus anticoagulant (LAC) were also measured. Patient groups compared were: 124 autoimmune disorders (40 ITP, 80 APLA, 24 multiple sclerosis, MS) and 54 hematologic disorders (35 thrombocytosis, 19 TTP).

RESULTS. (1) ITP (n=40, of which 19 were remission, 14 stable, 7 acute). Although APLA are known to be common in ITP, no relation to symptoms was identified. We discovered that APLA rise with onset of acute ITP, and decline or disappear in remission, p=0.007 [Br J Haem 128:366, 2005]. APLA was associated with bleeding, not thrombosis. (2) Multiple sclerosis (MS) (n=24, of which 7 were in remission, 24 exacerbation). APLA were known to be common in MS but no clinical correlations had been shown. We found that APLA in MS arise mainly in exacerbations, p=0.002, suggesting a link to the pathology. [Neurology 2005, 64(6, supl 1):A194.]. APLA in MS were exclusively IgM. (3) TTP (n=19). A role of APLA in TTP had been conjectured but evidence was equivocal. We found that 42% of acute cases were APLA+, and these had higher frequency of recurrence, p<0.05, and higher activation of platelets and endothelia (p=0.02) vs. APLA-. APLA declined with approach to remission. [Blood 2004, 104(11):242a.] APLA in TTP were exclusively IgG. (4) Thromocythemia (TC) (n=35, of which 14 had thrombosis (TB)). TC often entails TB. Recently APLA was implicated as a risk factor for TB in TC (Harrison et al). We confirmed and extended that work, finding APLA present in 66% of TC with TB, and that presence of APLA predicts TB, p<0.05. IgM was 2-fold more prevalent than IgG. Platelet activation was higher in TB cases, p<0.01. [Bidot et al, Hematol 2005, in press.] (5) Thrombosis (TB) in APLA (n=80 APLA+, of which 60 had TB). Many patients are APLA+ but free of symptoms. We found that APLA+ patients with TB had higher platelet activation than those without, p<0.05. In contrast, endothelial activation, although elevated in TB and non-TB, did not differ between these groups [Blood 104(11):143a, 2004].

CONCLUSIONS. These findings, together with work from others, point increasingly to a link between APLA and pathology in a wider range of inflammatory and hemostatic disorders than usually considered, not limited to thrombosis (TB). In autoimmune disorders such as ITP, MS and TTP, APLA tend to arise in exacerbation and remit in remission, suggesting role of APLA in exacerbation of autoimmunity and inflammation. Also of interest is our frequent finding of association between APLA and activated platelets and/or endothelium. Patterns appear disease-specific but specificity of the APLA involved may be subtle and beyond routine methods. Our findings suggest role of APLA in pathology is not limited to preponderately thrombotic disorders, but extends to other manifestations of autoimmune and inflammatory disorders. Clear understanding of meaning of APLA in these widespread associations could be of potentially great significance.