Treatment Strategies for GLILD in Common Variable Immunodeficiency: A Systematic Review.

Introduction: Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking. Goals: To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID. Methods: We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized. Results: 6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high. Conclusions: We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.

Immunoglobulin A and microbiota in primary immunodeficiency diseases.

PURPOSE OF REVIEW: With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients. RECENT FINDINGS: The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown. SUMMARY: Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency.