Viallard and colleagues describe an unusual case of extensive granulomatous disease in a woman with common variable immunodeficiency who had a large number of peripheral double-negative CD3 (⁺) T cells that displayed the phenotype and had a skewed variable gene segment usage. These authors suggest that the expansion of T cells could be viewed as a deviation brought about in compensation for the impaired T-cell immunity. Although the search for mycobacteria was not ultimately rewarded, it remains possible that a specific microbial species was responsible for this unusual T-cell expansion. Katial and colleagues [1] described a patient with common variable immunodeficiency who had a prominent expansion of peripheral blood T cells and an inverted ratio of CD4 to CD8 T cells in association with unexplained fever and pulmonary infiltrates. Granulomatous lesions were not identified in this case, but an immune-driven expansion of cells was also suggested. Nilssen and colleagues [2] found increased numbers of CD3⁺ T cells expressing the T-cell receptor in the intestinal tract of persons with common variable immunodeficiency and other B-cell defects, especially those with villous atrophy. An interesting aspect of Viallard and colleagues' case is the presence of prominent intestinal tract disease.

Zauber and coworkers describe a patient who, like one of our patients, had primary biliary cirrhosis with common variable immunodeficiency. We had previously reported one other case of biopsy-proven primary biliary cirrhosis in a woman with common variable immunodeficiency [3]. This woman was 61 years of age at presentation and had chronic pruritis, hepatomegaly, ascites, and peripheral edema. She died of coronary artery disease at age 63 years.

Since then, we have also seen a second patient: a 35-year-old man who had a history of Hodgkin disease, stage IV-B, that was treated with chemotherapy when the patient was 25 years of age. At age 29 years, abnormal liver function test results, present during chemotherapy, were investigated; liver biopsy confirmed primary biliary cirrhosis. The patient was positive for antimitochondrial antibodies (titer, 1:160) and began receiving ursodiol.

Two years later, immunoglobulin levels, which had been reduced for at least 8 years, were retested. The IgG level was 253 mg/dL, the IgA level was 22 mg/dL, and the IgM level was 72 mg/dL. Intravenous immunoglobulin therapy was started, and chronic bronchial and sinus infections improved. As was seen with the patient described by Zauber and colleagues, the antimitochondrial antibody titer decreased to 1:40 after intravenous immunoglobulin therapy began. Two years later, because of continued liver dysfunction and worsened liver histologic findings, methotrexate therapy, 15 mg/wk, was started. Two years after this therapy began, the patient developed sudden-onset pulmonary infiltrates and sensory changes; B-cell lymphoma involving the lungs and central nervous system was diagnosed. He died after autologous bone marrow transplantation. After our Annals report appeared, Mulligan and colleagues [4] reported that an uncommon tumor necrosis factor allele was more likely to be found in patients with common variable immunodeficiency who have granulomatous disease, suggesting a potential genetic mechanism for this phenotype. Because this phenotype seems to be associated with autoimmunity and tissue damage, its recognition is important.