MIXED MONOCLONAL CRYOGLOBULINEMIA AND MONOCLONAL RHEUMATOID-FACTOR CROSS-REACTIVE IDIOTYPES AS PREDICTIVE FACTORS FOR THE DEVELOPMENT OF LYMPHOMA IN PRIMARY SJOGRENS-SYNDROME
Ag. Tzioufas et al., MIXED MONOCLONAL CRYOGLOBULINEMIA AND MONOCLONAL RHEUMATOID-FACTOR CROSS-REACTIVE IDIOTYPES AS PREDICTIVE FACTORS FOR THE DEVELOPMENT OF LYMPHOMA IN PRIMARY SJOGRENS-SYNDROME, Arthritis and rheumatism, 39(5), 1996, pp. 767-772
Objective. To prospectively investigate whether mixed monoclonal cryog
lobulinemia (MMC) and monoclonal rheumatoid factor (mRF)-associated cr
oss-reactive idiotypes (CRD serve as predictive factors for the develo
pment of lymphoma in patients with primary Sjogren's syndrome (SS). Me
thods. One hundred three consecutive patients with primary SS were eva
luated from 1986 to 1991. In all patients, the amount of cryoglobulin
was measured by ultraviolet absorption at 280 nm and 260 nm. The type
of cryoglobulinemia was identified by agarose gel electrophoresis, com
bined with immunofixation. Sera from all patients were evaluated by en
zyme-linked immunosorbent assay, using the corresponding monoclonal or
polyclonal antibodies, for the presence of inmunoglobulins bearing th
e idiotypes 17109 (V kappa IIIb associated), G-6 (V(H)1 associated), a
nd 3rd SS (a rabbit polyclonal antibody raised against the Fab fragmen
t of an IgM kappa mRF from a patient with primary SS). Data analysis w
as performed by logistic regression. Results. Eighteen of the patients
with primary SS (17.4%) had MMC during the first evaluation. There wa
s a statistically significant correlation between the presence of MMC
and a higher prevalence of autoantibodies to Ro/SS-A and La/SS-B, as w
ell as extraglandular manifestations. During a 5-year period, 7 patien
ts developed lymphoma. Six of the 7 (86%) had MMC before the appearanc
e of lymphoma, compared with 12 of 96 (12.4%) of the remainder (r = 0.
421, P < 0.0009). Patients who developed lymphoma had higher amounts o
f cryoglobulin than those who did not (mean +/- SD 53.4 +/- 44.7 mg/dl
versus 26.8 +/- 20.6 mg/dl). CRIs 17109 and G-6 were also correlated
with lymphoma development (r = 0.321, P < 0.006 and r = 0.22, P < 0.03
, respectively). For both CRIs, this correlation was dependent on the
presence of MMC, since a stepwise multiple comparison analysis reveale
d that their individual significance was abolished when their correlat
ion with lymphoma in association with MMC was assessed. Conclusion. Th
e determination of MMC can be used as a laboratory predictive factor f
or lymphoma development in primary SS. CRIs 17109 and G-6 may also be
used to predict lymphoma development, especially when the monoclonal c
omponent is absent.