Rational Humoral immunodeficiency syndromes including common variable immune deficiency (CVID) are not uncommonly associated with autoimmune features seen in SLE. Studies were undertaken at an academic centre managing both disorders to determine the relative prevalence, clinical and immunologic features, and outcomes of SLE associated with humoral immunodeficiency.

Methods A retrospective review of records identified using an electronic medical record search of diagnosis codes for SLE and hypogammaglobulinemia seen between 2011 and 2016 was undertaken. The clinical and immunologic profile was determined for patients with confirmed or suspected SLE who also had undergone evaluation for humoral immunodeficiency.

Results We identified 40 patients meeting ACR criteria for SLE with inadequate response to pneumococcal vaccine challenge (failure to generate protective antibody titer to ≥5/14 pneumococcal vaccine antigens) and/or low serum IgG levels (<700 mg/dl) not attributable to antecedent immunosuppressive therapy. This comprised 5.0% of our SLE patients meeting ACR SLE criteria in active follow-up. An additional 37 patients with SLE clinical features but not meeting SLE ACR criteria were identified with low serum IgG and/or inadequate vaccine responses. Among the 40 identified patients meeting ACR SLE criteria, serum immunoglobulin levels ranged from 459–760 mg/dl; 36 (90%) had serum IgG levels <700 mg/dl, while 24 (60%) had inadequate response to pneumococcal vaccine challenge, including the four patients with serum IgG > 700 mg/dl. Frequent upper/lower respiratory infections requiring antibiotic treatment (≥3 episodes/year) were reported in 25/40 (63%) patients. SLE features developed 2–26 years (mean = 8.9 years) prior to the recognition of low serum IgG in 27 (68%) patients, whereas initial SLE features were noted concurrently with or 3–4 years following first confirmed low IgG levels in 13 (33%). Arthritis (75%), photosensitivity (81%), malar rash (63%) and mucosal ulcers (56%) were the most prevalent SLE features. Only 9 (23%) of patients had low complement C3 or C4 levels, 6 (15%) had cytopenias, and 2 (5%) had elevated levels of anti-dsDNA. The majority of patients were managed with antimalarials (86%), with 8/40 (20%) also using methotrexate; 18/40 (45%) were on treatment with IVIG and 6/40 (15%) were on treatment with belimumab. Disease activity was low (SLEDAI score ≤ 2) in 37/40 (93%) at the last noted follow-up assessment. In the four patients for whom sera was available for testing, levels of BLyS(BAFF) were elevated relative to those noted in 20 control patients without autoimmunity or immunodeficiency, but less than that noted in 20 SLE patients without noted humoral immunodeficiency.

Conclusion SLE may be a presenting feature of patients with humoral immunodeficiency. Serum immunoglobulin levels and assessment of the response to pneumococcal vaccination for patients with low or low normal serum IgG levels should be included as part of the evaluation for suspected SLE. Favourable outcomes are seen in the context of standard of care treatment for SLE combined with immunoglobulin replacement therapy and/or belimumab.