Isolated elevation of IgA anti-β2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients

Abstract

Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-beta(2)GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-beta(2)GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-beta(2)GPI antibody titres were 118.5 SAU (normal range: 0-20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-beta(2)GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-beta(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-beta(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-beta(2)GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-beta(2)GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

Live birth pregnancy outcome after first in vitro fertilization treatment in a patient with Systemic Lupus Erythematosus and isolated high positive IgA anti-β2glycoprotein I antibodies: a case report

“…A study by Lee SR et al showed that in sub-group of women with intra-uterine fetal demise and unexplained miscarriages who were previously negative for aPL antibodies, IgA anti-β2GPI was most commonly found [15]. Similar findings have been reported in case series of five patients with isolated elevation of IgA anti-β2GPI antibodies and history of unexplained recurrent abortion, intrauterine fetal death or preterm delivery because of pre-eclampsia [2]. Similarly, in a group of 36 women with unexplained recurrent abortions and negative for IgG anti-β2 GPI, the presence of isolated IgA-β2GPI was found in nearly 14% of these women [6].…”

“…Other conditions have also been described, such as unexplained recurrent spontaneous abortion/pregnancy loss, acute cerebral ischemia, cognitive dysfunction or transient ischemic attack [2]. IgA antiphospholipid antibodies are not currently recognized as formal laboratory criteria for antiphospholipid syndrome (APS), but according to the last international consensus guidelines on antiphospholipid antibodies (aPL), testing for IgA isotype is recommended for both anticardiolipin antibodies (aCL) and anti- β 2GPI when results of conventional markers (IgG and/or IgM isotypes) are negative and APS is still suspected [3].…”

Isolated IgA Anti-β2 Glycoprotein I Antibodies in Patients with Clinical Criteria for Antiphospholipid Syndrome

“…However, IgA aB2GPI antibodies have gained clinical relevance and were recently included as a clinic classification criterion for systemic lupus erythematosus [17]. Likewise, determination of IgA aB2GPI antibodies is recommended in patients with snAPS [21], LES, and in ethnics groups with a high prevalence of IgA isotype antibodies such as African Americans and long lasting SLE patients [18, 22]. …”

Challenges in the Diagnosis of the Antiphospholipid Syndrome

“…IgA anti-␤2GPI antibodies are frequently detected in specific ethnic groups such as African Americans (22 ). Case reports have been published of exclusive IgA anti-␤2GPI seropositivity with concomitant clinical manifestations (71 ).…”