ABSTRACT
We have analysed data from 150 patients initially classified as having CVID. About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoimmune disease. About 25% of CVID patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of CVID patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of CVID is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunodeficiency determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify CVID patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing CVID to specific subsets of patients.
