False-Positive Reactions for IgA Anti-Phospholipid and Anti-β2-Glycoprotein I Antibodies in Patients with IgA Monoclonal Gammopathy

Abstract

We report here that measurements of IgA anti-cardiolipin (aCL) and anti-β2-glycoprotein I (β2GPI) antibodies are unreliable in patients with IgA monoclonal gammopathies (MGs). MGs are characterized by monoclonal immunoglobulins produced by a proliferating B-lymphocyte clone. Monoclonal gammopathy of undetermined significance (MGUS) is the most common type of MG (1); the monoclonal component (MC) is IgA in 15–25% of MGs (2). aCL antibodies, originally described in patients with systemic lupus erythematosus (3), have been detected in patients with other autoimmune diseases (4)(5) and in the antiphospholipid syndrome (6)(7) as well as in nonrheumatologic disorders (8) and in healthy individuals (9)(10)(11). In patients with connective tissue diseases and antiphospholipid syndrome, aCL antibodies are most frequently IgG, followed by IgM. Kalunian et al. (12), however, reported a high incidence of IgA, rather than IgG-aCL antibodies associated with thrombosis and fetal loss, and other reports have suggested that IgA-aCL antibodies may have a clinical meaning even in the absence of IgG- or IgM-aCL (13)(14)(15)(16)(17)(18)(19)(20)(21). Their prevalence in healthy subjects seems negligible; in a series of 389 healthy pregnant women, Lynch et al. (22) found only one positive case (0.3%). Therefore, to properly assess the risk of thrombosis, thrombocytopenia, and recurrent abortions in systemic lupus erythematosus patients, the determination of IgA-aCL antibodies has been recommended (18)(21). Very recently, the same recommendation was also made for anti-β2GPI antibody determination because anti-β2GPI restricted to the IgA isotype can be found in the sera of systemic lupus erythematosus patients with thrombosis (23). IgG- or IgM-aCL activity has been described occasionally in subjects with MG (24)(25)(26)(27), but …