Rheumatology Advance Access originally published online on September 24, 2007
Rheumatology 2007 46(11):1657-1661; doi:10.1093/rheumatology/kem209
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Bone marrow B-cell clonal expansion in type II mixed cryoglobulinaemia: association with nephritis
Clinic of Rheumatology, DPMSC, 1Chair of Statistics, Department of Medical and Morphological Research, 2Laboratory, Department of Experimental and Clinical Pathology and Medicine, 3Department of Pathology, University of Udine and 4Department of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano (PN), Italy.
Correspondence to: S. De Vita, MD, Professor of Rheumatology, Head of the Clinic of Rheumatology, Azienda Ospedaliero-Universitaria, DPMSC, University of Udine, Italy, P.z.le S. Maria della Misericordia 1, 33100 Udine, Italy. E-mail: salvatore.devita{at}med.uniud.it
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Abstract |
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Objectives. To investigate the relationship between the pattern of bone marrow (BM) B-cell expansion and the clinical features of mixed cryoglobulinaemia (MC) syndrome.
Methods. Fifty-five patients with type II MC syndrome were analysed. Their median age was 64 yrs (range 24–82), the median disease duration was 6 yrs (range 1–26) and the mean follow-up after BM analysis was 2.65 yrs (S.D. = 1.33). Peripheral neuropathy was present in 33 patients (60%), nephritis in 14 (25.4%), skin ulcers in 14 (25.4%) and lymphoma or atypical lymphoproliferative disorder (LPD) in 17/55 (30.9%). Anti-HCV antibodies were found in 43/55 patients (78.2%). BM B-cell expansion was evaluated by a semi-nested PCR amplification of the V–D–J region of the IgH genes.
Results. A clonal B-cell expansion in the BM was found in 33/55 (60%) patients, while a polyclonal pattern in 22/55 (40%). A BM pattern of clonal B-cell expansion increased the risk of nephritis of about 10 times [odds ratio (OR) = 10.11, CI95%1.52–67.31], if compared to a polyclonal pattern. In contrast, the risk of skin ulcers was decreased in BM clonal cases (OR = 0.09, CI95%0.02–0.49). Overt lymphomas did not emerge from patients with BM monoclonal expansion (without clinical or histopathological features of lymphoproliferation; or with LPD) in a short-term, consistent with the finding that monoclonality was associated with nephritis and not with an underlying, not recognized lymphoma.
Conclusion. BM clonal B-cell expansion is associated with nephritis in MC syndrome. Particular B-cell clones may be preferentially expanded and may play a pathogenic role in MC nephritis.
KEY WORDS: Mixed cryoglobulinaemia, B-cell, Bone marrow, Nephritis, Lymphoma, Clonality
Submitted 19 March 2007;
revised version accepted 4 July 2007.
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