Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β₂ glycoprotein I domain 1 antibodies

Abstract

Objective The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities. Methods Healthy Sudanese pregnant women ( n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females. Results Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI ( p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. Conclusions IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

Validation of the Particle-Based Multi-Analyte Technology for Detection of Anti-PhosphatidylSerine/Prothrombin Antibodies

“…Our results are in line with a recent study by Elbagir and Colleagues [ 25 ], in which the authors assessed the performance of the PMAT system compared to EliA system, based on fluorescence enzyme immunoassay for the identification of different aPL isotypes in a large cohort of Sudanese and Swedish women [ 25 ]. While the need for routine testing for aPS/PT is still under debate, there is overwhelming clinical evidence that these antibodies are associated with thrombosis and pregnancy loss in patients with APS and that their presence increases the risk of developing such an event [ 21 , 26 , 27 ].…”

High IgA antiphospholipid autoantibodies in healthy Sudanese explain the increased prevalence among Sudanese compared to Swedish systemic lupus erythematosus patients

“…Our current data are, on the other hand, in agreement with our recent report showing an increase in IgA anti-β 2 GPI but not in IgA anti-D1 among healthy pregnant women in Sudan. 25 IgG anti-D1 is consistently reported to be accountable for APS-related events. 38 , 39 However, data on the significance of IgA/IgM isotypes are deficient.…”

“…This finding was not seen in Swedish healthy pregnancies and was not accompanied by a parallel increase in IgA anti-D1. 25 Moreover, in a former study on 89 Tunisian patients with inflammatory bowel diseases, a high prevalence of IgA anti-β 2 GPI, adjusted for total IgA, was reported using the 95th percentile of national controls. 30 A similarly high prevalence of IgA anti-β 2 GPI was also reported in primary biliary cirrhosis patients from the same country.…”

“…Specific analysis of the IgA isotype against D1 was performed in parallel with a previous study where a high prevalence of IgA anti-b 2 GPI was observed during apparently normal pregnancies in Sudan, as previously described. 25 Lupus anticoagulant (LA) was not included in this study due to difficulties in conforming to sample handling recommendations for LA testing in Sudanese SLE patients. 26 FEIA analyses were performed on different occasions in Sudanese and Swedish subjects, whereas PMAT and IgA anti-D1 analyses were performed in parallel.…”

Longitudinal Analysis of Anti-cardiolipin and Anti-β2-glycoprotein-I Antibodies in Recent-Onset Systemic Lupus Erythematosus: A Prospective Study in Swedish Patients

“…In addition, the presence of anti-β2GPI (all three isotypes) was suggested to be more common among Caucasians than African-Americans. In addition, a recent study has concluded that IgA aPL is more common in Sudanese patients with SLE than in Swedish patients with SLE ( 39 ). Furthermore, in the Sudanese control group, IgA aPL was more commonly detected than in the Swedish controls ( 22 ).…”