Lars Helgeland

Follicular lymphoma (FL) is a heterogeneous disease with some patients developing progressively or transformed disease early, whereas others follow an indolent clinical course. We evaluated the prognostic value of immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in FL patients. One hundred and four IGH sequences were obtained in tumour samples from 99 patients. The IGHV3 subgroup had the highest usage frequency (57.7%) with IGHV3-23 being the most common sequence. Patients with the IGHV5 subgroup or IGHV sequences from more than one subgroup had significantly less favourable prognosis with an estimated 5-year survival of 62.5 and 50.0%, respectively, as compared with a 5-year survival of 95.1% for patients with other IGHV subgroups (P=0.013 and P<0.001, log-rank). The poor survival associated with IGHV5 or >1 IGHV subgroup usage was an independent prognostic factor in Cox multivariate analysis (P=0.005). IGHV genes were unmutated showing >98% homology in 15.2% of cases. Contrasting the situation in chronic lymphocytic leukaemia (CLL), the presence of unmutated sequences did not yield prognostic information, although unmutated sequences were associated with age at diagnosis >60 years (P=0.022, Fisher's exact). In conclusion, our results indicate that analysis of IGHV gene usage might aid in predicting prognosis for FL patients.

Germinal center (GC)-like structures have previously been observed in minor salivary glands (MSG) of patients with primary Sjögren syndrome (pSS). The aim of our study was to explore the prevalence and features of GC-like structures and B cell clonality in patients with pSS with and without lymphoma. Based on a nationwide survey in Norway, we included 21 patients with pSS and with a concomitant lymphoma from whom MSG and/or lymphoma biopsies were available. Tonsil biopsies and MSG from 28 patients with pSS without lymphoma were used as controls. The presence of GC-like structures was investigated with H&E staining and double staining for CD21/IgD and CD38/IgD. B cell clonality in MSG and tumors were investigated with analysis of immunoglobulin gene rearrangements. H&E labeling of MSG revealed GC-like structures in 17/40 (43%) of the patients: 4/12 (33%) with and 13/28 (46%) without lymphoma. Staining for CD21/CD38/IgD demonstrated CD21+ networks in 27/40 (68%) of the patients. CD21+...

Background: Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) have modulating effects in several chronic infl amma- tory conditions. The aim of the present study was to test whether prior short-term dietary supplementation with n-3 (fi sh or seal oil) or n-6 (soy oil) PUFA rich oils would protect the development of dextran sulfate sodium (DSS)-induced colitis in rats. Methods: Forty-eight male Wistar rats were divided into 6 groups: no intervention, sham, DSS, seal oil + DSS, fi sh oil + DSS and soy oil + DSS. Following 7 days of acclimatisation, 1 mL oil (seal, fi sh or soy) or distilled water (sham) was administered by gavage day 8 to 14. Colitis was induced by 5% DSS in drinking water from day 15 to 21. Rats were sacri- fi ced on day 23. Histological colitis (crypt and infl ammation) scores, faecal granulocyte marker protein (GMP) and quan- titative fatty acid composition in red blood cells were measured. Results: Pretreatment with fi sh or seal oils did not signifi cantly infl u...

The accumulation of B cells in the thymus is a common feature of myasthenia gravis (MG). To understand whether factors enhancing B-cell survival are increased in MG, we studied the expression of APRIL, BAFF and three of their receptors in the thymus. In hyperplastic thymi, macrophages expressed APRIL and BAFF, and germinal-center B cells, BAFF-R. CD138-positive plasma cells were abundant in MG thymi. By contrast, BCMA-positive plasma cells were scarce. The expression of APRIL and BAFF in MG thymi may reflect the establishment of an environment favorable to B-cell survival.

Chronic inflammation of the intestinal wall is the common characteristic of Crohn's disease and ulcerative colitis; disorders, which in some cases can be difficult to distinguish. The inflammation also affects the local neuronal plexuses of the enteric nervous system. It is known that plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) are upregulated in neurons after experimental peripheral nerve injury and have been linked to nerve regeneration. The expression of PAI-1 and uPAR in neuronal cells in lesions of the gastrointestinal tract was analyzed by immunohistochemical techniques. PAI-1 was found in a subset of neurons primarily located in the submucosal plexus of the small and large intestine in 24 of 28 cases (86%) with Crohn's disease, but in none of 17 cases with chronic ulcerative colitis and other severe inflammatory conditions in the intestinal wall. The PAI-1 was seen in the perikarya of the neurons and a few proximal axons, whereas nerves were negative. uPAR was seen in nerves in all types of lesion varying from 21% to 88% of the cases, most frequent in colon adenocarcinomas. No uPAR-positive nerves were detected in normal colon. PAI-1-positive neurons in inflammatory bowel disease are linked to chronic inflammation in Crohn's disease, implying PAI-1 as a potential parameter for the differential diagnosis between Crohn's disease and ulcerative colitis. The findings also suggest that PAI-1 in neurons is related to pain and that both PAI-1 and uPAR are involved in neuronal repair in the inflamed tissue.