The biological basis for current treatment strategies for granulomatous disease in common variable immunodeficiency.

PURPOSE OF REVIEW: The pathogenesis of granulomatous disease in common variable immunodeficiency (CVID) is still largely unknown, which hampers effective treatment. This review describes the current knowledge on the pathogenesis of granuloma formation in CVID and the biological basis of the current treatment options.

RECENT FINDINGS: Histological analysis shows that T and B cells are abundantly present in the granulomas that are less well organized and are frequently associated with lymphoid hyperplasia. Increased presence of activation markers such as soluble IL-2 receptor (sIL-2R) and IFN-ɣ, suggest increased Th1-cell activity. Moreover, B-cell abnormalities are prominent in CVID, with elevated IgM, BAFF, and CD21low B cells correlating with granulomatous disease progression. Innate immune alterations, as M2 macrophages and neutrophil dysregulation, indicate chronic inflammation. Therapeutic regimens include glucocorticoids, DMARDs, and biologicals like rituximab.

SUMMARY: Our review links the biological context of CVID with granulomatous disease or GLILD to currently prescribed therapies and potential targeted treatments.