Background/Purpose: APS ACTION International Clinical Database and Repository was created to study the natural course of disease over 10 years in persistently antiphospholipid antibody (aPL)-positive patients with/without other systemic autoimmune diseases (SAIDx). Although, IgA aCL and IgA aβ₂GPI were included in the new SLICC systemic lupus erythematosus (SLE) classification criteria, the prevalence and clinical significance of IgA isotype have been controversial. Thus our objective was to better define the prevalence and clinical significance of IgA aCL and aβ₂GPI in aPL-positive patients with/without SLE.

Methods: A web-based data capture system is used to store patient demographics, aPL-related history, and medications. The inclusion criteria are positive aPL based on the Updated Sapporo classification criteria at least twice within one year prior to enrolment. Patients are followed every 12±3 months with clinical data and blood collection. The baseline samples are analysed in the APS ACTION core laboratories to confirm aPL-positivity. For this cross sectional study, using chi square test, we compared the demographic and clinical characteristics of aPL-positive patients with/without SLE based on different aCL/aβ₂GPI isotypes.

Results: As of April 2016, 638 aPL-positive patients recruited from 24 centers; 489 (77%) had core laboratory assessments of IgG/M/A aCL/aβ₂GPI. Forty-two patients were excluded due to the diagnosis of a SAIDx other than aPL/APS and/or SLE. Thus, 320 (72%) aPL-positive patients without SLE (258 [81%] with APS) and 127 (28%) with SLE (96 [76%] with APS) were analyzed. The frequency of aCL and aβ₂GPI IgG/M/A positivity (defined as > 20U) was not different between the two groups except the IgG isotype, which was more common in aPL-positive patients without SLE (53% vs 42% [p: 0.03] for aCL and 38% vs 21% [p: 0.03] for aβ₂GPI). However, the frequency of IgA aβ₂GPI positivity was 3-fold higher than IgA aCL positivity (33% vs 11% [p<0.001] in those with SLE, and 32% vs 12% in those without SLE [p<0.001]). The demographics and aPL-related clinical manifestations were not different among aCL/aβ₂GPI IgG, IgM, and IgA isotypes (Table). The results were similar when the aCL/aβ₂GPI ELISA cut-off was set to 40U. Of note, the frequency (%) of isolated aCL IgG/M/A- and aβ₂GPI IgG/M/A-positive patients (independent of the LA status) were 22/19/1 and 11/11/8, respectively (when the ELISA cut-off was set to 20U); isolated aβ₂GPI IgA positivity was significantly higher in aPL-positive patients with SLE, compared to those without SLE (p: 0.006).

Conclusion: Although IgA aβ₂GPI positivity is more common than IgA aCL positivity, especially in SLE, the aCL/aβ₂GPI IgA isotype does not distinguish between aPL-positive patients: a) with/without SLE; and b) with different aPL-related clinical events.

Table: Clinical features of All IgG, IgM and IgA aPL positive patients, cut-off aPL ELISA ≥20u.

 *Sapporo Classification Criteria not met