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

Sahwa Elbagir,Iva Gunnarsson,Nasreldeen A Mohammed,Amir I Elshafie,Musa Am Nur,Eleftheria Pertsinidou,Elnour M Elagib,Mawahib Ie Aledrissy,Vivek Anand Manivel,Elisabet Svenungsson,Johan Rönnelid

doi:10.1177/0961203320945387

Sahwa Elbagir, Iva Gunnarsson + Show 9 more

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https://doi.org/10.1177/0961203320945387

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Abstract

ObjectivesIgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs.MethodsConsecutive SLE patients and age- and sex-matched controls from Sudan (N = 115/106) and Sweden (N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome–related events were obtained from patients’ records. IgA/G/M anticardiolipin and anti-β2 glycoprotein I (β2GPI) were analysed with two independent assays. IgA anti-β2GPI domain 1 (D1) was also investigated. Manufacturers’ cut-offs and the 95th and 99th percentile cut-offs based on national controls were used.ResultsSudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers’ cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-β2GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts.ConclusionsIgA anti-β2GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers’ cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach.

Highlights

IgG and IgM anticardiolipin and anti-b2 glycoprotein I (b2GPI) are included in the 2006 revised Sapporo classification criteria for antiphospholipid syndrome (APS),[7] whereas IgA aPL were added as laboratory parameters to the 2012 Systemic Lupus International Collaborating Clinics (SLICC)/ American College of Rheumatology (ACR)[8] as well as the recent European League Against Rheumatism EULAR/ACR systemic lupus erythematosus (SLE) classification criteria.[9]
We investigated and compared the prevalence and clinical significance of aCL and b2GPI isotypes among SLE patients from Sudan and Sweden applying analogous methodology including assays and cut-offs used
We detected that high IgA aPL levels and positivity was common among Sudanese patients using manufacturers’ cut-offs

Summary

Introduction

Antiphospholipid antibodies (aPL) are present in 20– 30% of systemic lupus erythematosus (SLE) patients,[1] where IgA anti-b2 glycoprotein I (b2GPI) is reported to be a highly frequent isotype.[2,3,4,5,6] Only IgG and IgM anticardiolipin (aCL) and anti-b2GPI are included in the 2006 revised Sapporo classification criteria for antiphospholipid syndrome (APS),[7] whereas IgA aPL were added as laboratory parameters to the 2012 Systemic Lupus International Collaborating Clinics (SLICC)/ American College of Rheumatology (ACR)[8] as well as the recent European League Against Rheumatism EULAR/ACR SLE classification criteria.[9]. A positive association with APS-related events was demonstrated in several studies for both IgA aCL2,3,10 as well as IgA anti-b2GPI.[2,4,11,12,13] other investigators could not confirm these associations.[3,10,14,15] Interpretation of data provided by previous studies on aPL in general and IgA aPL in particular and the relationship to APS features is rather complex. Insufficient standardization of IgA aPL assays contributes to this enigma, heterogeneity was evident when comparing different diagnostic kits.[16,17,18] In addition, the frequent co-occurrence of other isotypes with IgA makes it even more troublesome to ascertain the individual role of IgA aPL in SLE

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