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Medical Research Society Antibody Fc portions can interact with cell surface proteins termed Fc receptors (FcRs). We have examined the expression of FcRs on cultured human mesangial cells (HMCs) as these receptors may be involved in the modulation of glomerular inflammation. IgAtontaining immune complexes are deposited in the mesangium in IgA nephropathy (IgAN). Fc alpha RI (CD89) has been implicated in the pathogenesis of IgAN and cultured HMCs are reported to bind IgA. However, whether HMCs express CD89 is controversial. Here, expression of CD89 was examined using RT-PCR and western blotting. CD89 was not detected either on rating HMCs or following stimulation of HMCs with IL-I and TNFa or with dibutyrl cyclic AMP (dbcAMP). A novel FcR, which binds IgA and IgM, was recently described on murine macrophages and B lymphocytes. We detected RNA transcripts for the human homologue of this Fc alphdmu receptor in all of 6 HMC lines examined. Expression was upregulated following stimulation with IL-l and TNFa. This new IgA binding receptor may be involved in the pathogenesis of IgAN. The presence of Fc receptors for IgG was examined using RT-PCR. Transcripts for the high affinity receptor CD64, and the various forms of the low affinity receptors, CD32 and CD16, were not detected on any HMCs. Expression was not induced following stimulation of HMCs with either IL-1 and TNFa or with dbcAMP. The Fc gamma chain, an accessory molecule required for expression and signal transduction by several FcRs was not detected either. In summary, HMCs were found to express transcripts only for a novel IgNIgM FcR. This receptor is upregulated by inflammatory cytokines and may be responsible for glomerular IgA immune complex deposition in IgA nephropathy. M2 I PLASMA OUABAIN LIKE SUBSTANCEAND PLATELET SODIUM PUMP ACTIVITY IN CHRONIC RENAL FAILURE 9P M22MICROBIAL CELL WALL OLIGOMANNAN INHIBITS NEUTROPHIL CHEMILUMINESCENCE: A POSSIBLE MECHANISM FOR GRANULOMA FORMATION IN CROHN'S DISEASE? C M MPOFU, JM MODES, and SW EDWARDS Department of Medicine and School of Biological Sciences, University of Liverpool, Liverpool L69 3GA Background crohn's l i e intestid lesions OCCUT in Chronic ~ u l o m a t t w s Disease, a condition caused by a defea in phagacyte fimction. C r o b disease patients commonly have serum antibcdies to baker's yeast (Socchmmyces cerevrsiw). The epitope for this antibody is oligomannan which is present in t m e r i a l and yeast cell walls. Our hypothesis is that oligomannan, shed by intramud bacteria, may inhibit neU(r0phil function within the mucosa, leading to the granulomatous lesions seen in CD.Methods The effect of S. cerevesiae oligomannan on phorbol ester @MA) induced-rrspiratoryburst of neutmphils from healthy volunteers was measuTed by luminol-ampliliedor isoluminol-amplified chemiluminescemz. Neutrophils were isolated using a onestep o -n method and suspended in HBSS buffer R s u ~ . I I Oliomannan decreases the neutrophil 3 0.lZhg 0.25nq 1 0.- Oligomannan dose (mghl) At the highnt concenlration used (1 mg/mL), oligomannan idubited luminol dependent chemiluminescence by 68 % (rt 5 "/4 n = 6). Luminol chemilumkscence measures the combined activities of the neutrophil NADPH oxidas and myeloperoxidas, and so the oligomannan could be acring on either or both of these activities Hower, oligomannan (at 1 mg/mL) also inhibited PMA-stimulated isolnminol-amplifiedchemilumin-ce by 54.9% (* 10%). As isoluminol largely measures superoxide secretion, the oligomannm may have an effect on NADPH oxidase activity, or scavenge extracellularoxidants. Concludon S cerevesrue oligomannan causes dose-related inhibition of the PMA-induced respiratory burst This supports the hypothesis that microbial oligomannaos impair m u d phagocyte function, thus generating the granulomatous phenotype of Crohn's disease. F FONG, A BUTT, D GOLDSMITH and R SWAMINATHAN* M23 COELIAC DISEASE AND THE CTLA-4/CD28 GENE Department of Chemical Pathology and Renal Medicine Guy'and St Thomas' Hospitals Trust Chronic renal failure (CRF) is associated with reduction in the activity of Na,K-ATPase. There is a suggestion that this reduction in activity may, in part, be due to the presence of endogenous sodium transport inhibitor(s). An example of one such inhibitor is the recently identified ouabain-like substance (OLS). Using a ouabain radioimmunoassay, we have previously shown that serum and urine OLS increase on sodium loading. In the present study the relationship between serum OLS and platelet Na', K'-ATPase activity was investigated. Five groups of subjects comprising (A) healthy individuals (n=ll), (B) CRF patients on dialysis @=lo), (C) patients on haemodialysis (n=lO), @) peritoneal dialysis (CAPD, n=14) and (E) patients after renal transplant (n=15) were examined. Subjects were well matched for relevant clinical parameters (e.g. age, sex, BMI and plasma sodium concentration), with the exception of groups D (range 39 - 76 years) and E (range 38 - 81 years) who were significantly older group A (range 21 - 56 years). Platelet Na', K' ATPase activity was lower (51.7* 6.8 Wgpr) and plasma OLS (0.35* 0.03 nmol/L) was higher in group C compared to that in group A ( 7 3 3 5.2 U/gpr, 0.26* 0.05 nmovL). Platelet Na', K'-ATPase activity showed a strong and significant inverse correlation with plasma OLS concentration (r = -0.855, p < 0.05). Surprisingly, Na', K'ATPase activity remained depressed and OLS increased significantly after 4 hours of haemodialysis, whereas the converse may have been expected. The results suggest that the reduction in sodium pump activity is associated with high OLS. REGION: EVIDENCE FOR ASSOCIATION IN UK FAMILIES AL KING, SJ MOODIE, JS FRASER, D CURTIS, E REID, AM DEARLOVE, and PJ CICLITIRA' GastroenterologyUnit, GKT, The Rayne Institute, St Thomas' Hospital, London SEI 7EH Background Susceptibilityto coeliac disease (CD) has a strong genetic component, with a known association with certain HLA-DQ alleles. However this accounts for only a proportion of the heritability, and it is likely that other non-HLA genes are involved in disease development. Association of CD with a locus on chromosome 2q33, which contains the cytotoxic T-lymphocyte associated (CTLA-4)gene and the CD28 gene has been demonstrated in a number of European populations, but not in others. Aim Our aim was to investigate this gene region in UK coeliac families using an association study design. Methods We genotyped 166 families for 6 microsatellitemarkers spanning 3cM of the CTLA-4/CD28 gene region. One hundred and forty-two ofthese families were also genotyped for 2 single nucleotide polymorphisms (SNPs) in the CTLA-4 gene, one at position +49 (A/G)in exon I, and the other at position -3 18(CTT), in the promoter region. Data for biallelic markers were analysed using the transmission disequillibriumtest (TDT).Multiallelic data were analysed using the ETDT program, which carries out a logistic regression analysis to determine whether different marker alleles vary in terms of their probability for being transmitted from a heterozygous parent to an affected offspring. Results The SNPs showed no evidence of association,and these two polymorphisms are unlikely to account for disease susceptibility. There was, however, significant evidence for associationbetween CD and the D2S2214 microsatellite marker (x2=19.4,7df, p=0.007).The major contributionto this associationwas made by allele *278,which was transmitted from 92 heterozygous parents and not transmitted from 49 (x2 =I 3. I , 1 df, p=0.0003). Conclusion The results support the findings of other European studies, and suggest that an important non-HLA susceptibility locus lies within this region.