Common variable immunodeficiency disorders (CVID) are a group of
rare diseases of the immune system and the most common symptomatic
primary antibody deficiency in adults. The "variable" aspect of CVID refers to the approximately half of the patients who develop non-infective complications, mainly autoimmune features, in particular organ specific
autoimmune diseases including
thyroiditis, and
cytopenias. Among these associated conditions, the incidence of
lymphoma, including mucosal associated lymphoid tissue (MALT) type, is increased. Although these associated autoimmune disorders in CVID are generally attributed to
Systemic Lupus Erythematosus (SLE), we propose that
Sjogren's syndrome (SS) is perhaps a better candidate for the associated disease. SS is an autoimmune disorder characterized by the lymphocytic infiltrates of lacrimal and salivary glands, leading to dryness of the eyes and mouth. Thus, it is a lymphocyte aggressive disorder, in contrast to SLE where pathology is generally attributed to auto-antibody and complement activation. Although
systemic lupus erythematosus (SLE) shares these features with SS, a much higher frequency of
MALT lymphoma distinguishes SS from SLE. Also, the higher frequency of germ line encoded
paraproteins such as the monoclonal
rheumatoid factor found in SS patients would be more consistent with the failure of B-cell VDJ switching found in CVID; and in contrast to the hypermutation that characterizes SLE
autoantibodies. Thus, we suggest that SS may fit as a better "autoimmune" association with CVID. Examining the common underlying biologic mechanisms that promote lymphoid infiltration by dysregulated lymphocytes and
lymphoma in CVID may provide new avenues for treatment in both the diseases. Since the diagnosis of SLE or
rheumatoid arthritis is usually based on specific
autoantibodies, the associated autoimmune features of CVID patients may not be recognized in the absence of
autoantibodies.