Background/Purpose:  Infection is a major cause of mortality in all stages of SLE. This is likely multifactorial in nature. We hypothesized that some patients with SLE have acquired immunoglobulin deficiency, which may put them at higher risk of infection. We aimed to examine the association and prediction of immunoglobulin levels and the risk for severe infections in lupus patients

Methods:  Patients with SLE have been followed prospectively at 2-6 month intervals according to a standard protocol, which includes detailed clinical and laboratory assessments including immunoglobulin levels and recording of infections. All information is recorded in the Clinic database. Damage accrual was measured by the SLICC/ACR damage index (SDI). Included in this study were patients with severe infections, defined by either requiring parenteral antibiotics or 3 infections within 2 years. Controls were patients followed for the same period who did not have infections. Immunoglobulin levels were recorded as low, normal, or high according to the laboratory standard. Persistently low immunoglobulins were defined as two or more low consecutive measurements. Logistic regression analysis was performed to determine first the factors associated with infection and then factors predisposing to severe infection.

Results:   We first identified from the database 250 patients with severe infections and 381 patients without infection. Patients with severe infections had lower IgG and IgA levels, and were treated with higher doses of glucocorticoids (GC). Logistic regression analysis revealed that age at SLE diagnosis (OR 1.019 95% CI 1.004,1035, P=0.014), low IgM levels (OR 2.175 95% CI 1.114, 4.245, p = 0.0228) and GCS dose (OR 1.079 95% CI 1.058, 1.101, p = <0.001) were associated with infection, adjusted for other demographic and clinical variables. We then examined 148 patients with persistently low immunoglobulins and no infection at first measurement and compared them to 430 controls for infection outcome. The low immunoglobulin group had more severe infections, higher SDI score, higher GC and immunosuppressive use. Logistic regression analysis revealed low IgG levels (OR 3.546 95% CI 1.852, 6.787, p = 0.0001), low IgM levels (OR 2.209 95% CI 1.274, 3.83, p = 0.0048), female gender (OR 2.285 95% CI 1.019, 5.125, p = 0.045), SDI (OR 1.188 95% CI 1.029, 1.373, p = 0.019) SLE duration (OR 1.056 95% CI 1.03, 1.084, p = <0.0001) to be predictors for severe infection and antimalarial treatment to be protective (OR 0.566 95% CI 0.355, 0.902, p = 0.0166) after adjustment for other demographic and clinical variables.

Conclusion:   Our study shows consistent association between low immunoglobulin level and clinically significant infection in lupus patients. Furthermore, low IgG and IgM levels increase the risk of severe infection, while antimalarial treatment is protective. Thus immunoglobulin assessment should be performed routinely in patients with SLE.  

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunoglobulins-level-and-risk-of-infection-in-systemic-lupus-erythematosus/