Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus

Abstract

Objective. To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection.Methods. Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = lo), and in those with syphilis (n = 15) by enzymelinked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of p2-glycoprotein I (p2-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity.Results. Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of &GPI as a binding cofactor, similar to aCL found in Conclusion. The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.Human infection with parvovirus B19, a small, single-stranded DNA virus, is associated with a variety of clinical manifestations, including rash, arthralgia, thrombocytopenia, leukopenia, fetal wastage, hypocomplementemia, autoimmune hemolytic anemia, and vasculitis (1-3). In addition, infection can be associated with elevated levels of autoantibodies to nuclear components (antinuclear antibodies [ANA]), doublestranded DNA (dsDNA), lymphocyte antigens, neutrophi1 cytoplasmic antigens, and cardiolipin (1-4).The prevalence and specificities of anticardiolipin antibodies (aCL) in B19 infection are not known. Raised levels of antiphospholipid antibodies (aPL) or aCL have been reported in a variety of other infections, including chicken pox, hepatitis A, infectious mononucleosis, rubella, adenovirus, mumps, and human immunodeficiency virus (HIV) (5), and are also well recognized in syphilitic infections (6). In light of the similarity of some of the clinical features presented by parvovirus B19 infection with those of autoimmune connective tissue diseases, we were interested in determining if the aCL antibodies observed in B19 infection were similar to those found in systemic lupus erythematosus (SLE) and whether similar antibodies were found in patients with acute viral infections other than parvovirus B19. One distinguishing feature of aCL found in au...

Bacterial induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome

“…Hojnik et al (30) found increased levels of anti-β2GPI Ab's in a significant proportion of leprotic patients, an observation that was confirmed by other investigators who indicated that these β2GPI-dependent aPLs were associated with thrombosis in leprosy (31). In another study, parvovirus B19-associated aCL Ab's were shown to be β2GPI dependent and behaved in a fashion similar to the autoimmune aPLs (32). Furthermore, some cases of viral hepatitis C-associated aPLs have been reported to be complicated with thrombosis (33).…”

Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus‐derived peptide cause thrombosis and activation of endothelial cells in vivo

“…Other investigators have shown that these ␤ 2 GPI-dependent aPL were associated with thrombosis in leprosy (53). In another study, parvovirus B19-associated aCL antibodies were shown to be ␤ 2 GPI dependent and to behave in a manner similar to that of "autoimmune" aPL (51). Furthermore, some cases of viral hepatitis C-associated aPL have been reported to be complicated with thrombosis (48).…”

“…Recently, the belief that infection-associated aPL are ␤ 2 GPI-independent, do not bind ␤ 2 GPI in the absence of phospholipids, and are not associated with thrombosis or other clinical complications of APS has been challenged in a significant number of reports (50)(51)(52). In one study, aCL present in leprosy patients were shown to be heterogeneous with respect to their ␤ 2 GPI requirement: in 10 of 31 leprosy sera, the aCL were ␤ 2 GPI dependent, and 21 of 31 did not require ␤ 2 GPI for binding to CL (50).…”

Biosensor Analysis of β2-Glycoprotein I–Reactive Autoantibodies: Evidence for Isotype-Specific Binding and Differentiation of Pathogenic from Infection-Induced Antibodies

“…Some studies, however, have indicated that antibodies against ␤2GPI can also be found in patients with parvovirus B19, leptospirosis, syphilis, and other infections (25)(26)(27). Because these patients did not show clinical signs of APS, the specificity of anti-␤2GPI detection by ELISA is questionable.…”