Background/Purpose: Systemic Lupus Erythematosus (SLE) is known to be associated with deficiency of C1q, C4, and C2. There is high frequency of discoid lesions (2.7%) and SLE (0.5%) in Chronic Granulomatous Disease (CGD). Selective IgA Deficiency (SIgAD) has been associated with juvenile (5.2%) and adult (2.6%) SLE. About 25% of patients with Common Variable Immunodeficiency (CVID) develop autoimmune manifestation, including SLE. Although there are reports of individual primary immunodeficiency (PID) in SLE, there is no systematic study estimating the fraction of SLE adult patients presenting any form of PID. This study aimed to estimate the prevalence of overall PID in a cohort of SLE patients and healthy controls, and to compare the clinical characteristics of the SLE patients with and without PID.

Methods: 300 SLE patients (ACR criteria) and 301 controls (blood donors) underwent clinical examination and were evaluated for total hemolytic complement (CH50), C2, C3, C4A and C4B  gene copy number, immunoglobulin isotypes and IgG subclasses, as well as quantification of the oxidative burst in neutrophils. Patients who presented any laboratory indication of PID underwent a novel examination after 60 days for confirmation. Patients with active disease and abnormal results were followed and underwent novel tests after the end of the flare or excluded if no remission was attained up to the end of the study. Cases with low C2 serum levels underwent C2 gene analysis by PCR for confirmation. Those who presented altered unexplained CH50 underwent C1q determination. Those with C4A and/or C4B low copy number had C4 serum levels determined. Diagnosis of PID was established according to “2009 International Union of Immunological Societies Expert Committee on PID”.

Results: There were 84 SLE patients (28%) and 10 controls (3.33%) with established diagnosis of PID (p<0.001). SLE patients had a significantly (p<0.01) higher frequency of IgG₂ deficiency (n=37; 12.3%), IgG₃ deficiency (n=24; 8%), IgG₄ deficiency (n=11; 3.6%), and IgM Deficiency (n=24; 8%) as compared to HC (0.3%, 0%, 0%, and 1.6%, respectively). One female patient presented neutrophil oxidative burst profile compatible with CGD gene carrier status (0.33%). There were no cases of C2, C3, C4 or C1q deficiency, CVID, CGD, Hyper-IgM and Hyper-IgE syndromes. Patients with IgG₃ or IgG₄deficiency presented higher frequency of lupus nephropathy and those with IgM deficiency presented higher prevalence of oral ulcers. Overall PID was not associated with most SLE clinical manifestations, infection rate, immunosuppressant use, age at disease onset, disease duration, comorbidity, SLEDAI and SLICC-DI.

Conclusion: Over one quarter of SLE patients presented some form of PID, largely represented by immunoglobulin deficiency. Due to the important role of immunoglobulins in the clearance of immunocomplex, apoptotic bodies and pathogens, low levels of these components might induce a state of frequent and persistent immunological stimulation, which may foster autoimmunity development in genetically predisposed individuals. Our results suggest that an underlying immunodeficiency state may be involved in the disease pathophysiology in a substantial fraction of SLE patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serial-screening-shows-that-28-of-systemic-lupus-erythematosus-adult-patients-carry-an-underlying-primary-immunodeficiency/