Histopathological analysis of the MSG biopsies from 48 patients with pSS showed a different degree of FLS, defined as focus score, for those with normal biopsy, or abnormal, as indicated in Table 1. Histopathological analysis of labial biopsies of 40 control subjects show different degrees of CS, as shown in Table 4. We observed that 40% of pSS

patients with FLS < 1 showed clonal IgH rearrangements compared with patients who had an abnormal biopsy (FLS ≥ 1), in some cases reaching 100%, as shown in Table 4. This difference was statistically significant (P < 0·01; χ2 test, 99% CI). In addition, we determined that 83·4% of the cases with pSS presented an oligo–monoclonal IgH rearrangement Rapamycin cost compared with 19% of the cases diagnosed with CS. There was a high correlation in control cases between the severity of CS and the presence of B cell clonality (Table 4). Seven VX-809 datasheet cases with severe CS showed B cell oligo–monoclonality compared with those diagnosed with mild to intermediate CS (87·5 versus 3·1%; P < 0·01; χ2 test). The biopsy was completely normal in only two cases and we did not detect a clonal IgH gene rearrangement by PCR (Table 4). Our results showed 58% and 79% of B cell clonality or oligoclonality, respectively, in the MSG of SS patients using FR3/LJH and FR2/LJH-VLJH primers. Similar results have been reported in the literature, where 77% of cases with NHL were PCR-positive, arguing that the

low detection of clonal B cells is due to partial rearrangements, inversions, somatic mutations or deletions

that can be missed by PCR [26]. The addition of FR1c-LJH primers to our PCR analysis allowed a higher detection rate of SS cases, as reported previously by Aubin and co-workers [17]. Therefore, the use of the three sets of primers diminished the false negative results and improved the detection rate in 86·7% of the SS patients (Table 3). Also, we observed that the addition of FR3 did not increase the number of positive cases, therefore the failure of FR3 or FR2 to detect clonality in some cases could be the acquisition of somatic mutations in the primer target sequences, due to mispriming during the PCR [11,12,15,26]. Another possibility is that the IgH gene rearrangement is related closely to the cellular triclocarban origin involved in the lymphoid pathology. In these cases, absence of clonality for the FR3-VLJH primers would indicate the presence of post-GC B cells or memory B cells in the salivary glands, characterized by cells bearing somatically hypermutated VH genes, as has been found in a series of studies in NHL and MALT [10,28,29]. It has been determined that patients with SS have a 16-fold increased risk of developing lymphoma [5,30]. Several studies have suggested that lympho-epithelial lesions in SS patients show a high presence of clonal expansion of B cells, as determined by molecular analysis of the IgH rearrangement, morphological or immunophenotypic determination.