Background/Purpose: Microchimerism with HLA mismatched maternal cells can be readily demonstrated in normal individuals and is now established as a normal biological phenomenon.  Pediatric SLE patients have decreased levels of blood maternal microchimerism, suggesting a loss of T-cell tolerance to maternal antigens.   Because maternal MHC molecules are the most likely targets of the T-cell hyperactivity, we reasoned that pediatric lupus patients may also have B cell reactivity to maternal MHC.  

Methods:

To test for loss of B-cell tolerance to maternal MHC, we measured IgG specific for HLA Class II antigens in plasma samples from children who have never been pregnant:  81 with SLE (49 (60%) with active disease, SLEDAI >4), 20 patients (24%) with nephritis.   Control groups consisted of 16 systemic sclerosis (SSc), 20 juvenile idiopathic arthritis (JIA), and 78 healthy children.  OneLambda, Inc. LABScreen microbeads coated with purified Class II HLA antigens were used to detect specific IgG. Data acquisition and analysis was performed using LABScan™ Statistical analysis was performed using SPSS version 16.0, Mann Whitney was used to determine median difference between groups, Correlations were tested by Spearman and associations by Likelihood ratios or Fisher Exact Test, ROC curves were constructed to test for the specificity of HLAab for lupus diagnosis and active lupus. 

Results: All Subjects:  The median values of 90% of specific HLAab were high in patients with SLE compared to controls.  HLAab levels in JIA and SSc were similar to controls. Among the SLE patients, 27 out of 77 HLA antigens were increased in patients with active disease compared to those without active disease.  Of these, a significant association was found with disease activity in 15 HLAab (see Table 1).  ROC curves demonstrated specificity for active SLE in 4 HLAab, with AUC >.700: DQA1*0301-DQB1*0302 (AUC .758, 95% CI 0.66-.86, p<0.001), DQA1*0301-DQB1*0303, (AUC 0.76, 95% CI 0.66-.87, p<0.001), DQA1*0501-DQB1*0201 (AUC 0.73, 95% CI 0.61-.84, P=0.001, and DPB1*1401=DPA1*0201 (AUC 0.72, 95% CI 0.6-.84], P=0.001. Ten HLAab demonstrated a significant median difference between those with and without nephritis, and seven of those showed significant associations (Table 1).

Conclusion:

Children with SLE have high values and a considerable number of anti-HLA class II autoantibodies which seem to be specific, related with disease activity and to a lesser extent with nephritis.   If confirmed, HLAab could represent useful biomarkers for disease activity. 

Table 1. Significant association between HLAab with Disease Activity and Nephritis

Associations between Disease Activity (SLEDAI>4) and Nephritis with HLAab are reported as Likelihood Ratios and Fisher Exact Test^&

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-histocompatibility-antigens-in-juvenile-systemic-lupus-erythematosus-patients/