Bone marrow B-cell clonal expansion in type II mixed cryoglobulinaemia: association with nephritis.
OBJECTIVE
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.


CONCLUSIONS
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.
Quartuccio
L
L
Clinic of Rheumatology, Azienda Ospedaliero-Universitaria, DPMSC, University of Udine, Italy, P.z.le S. Maria della Misericordia 1, 33100 Udine, Italy.
Fabris
M
M
Salvin
S
S
Isola
M
M
Soldano
F
F
Falleti
E
E
Beltrami
C A
CA
De Re
V
V
De Vita
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002455:Cell Division; D002999:Clone Cells / Q000276:immunology; D003449:Cryoglobulinemia / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000276:immunology; D012883:Skin Ulcer / Q000276:immunology