Syftet med studien var att studera effekterna av några miljöfaktorer och genetiskt predisponerande faktorer för reumatoid artrit (RA). RA är en inflammatorisk sjukdom där immunsystemet bryter ner kroppsegen vävnad. En signifikant ökad risk för RA påvisades vid exponering för spannmålsdamm och rökning. Generna som studerades var GSTM1, GSTT1 och Fc-gamma-RII. Generna i sig var ingen predisponerande faktor för RA, men rökning visade sig vara en signifikant högre riskfaktor för de som hade en deletion av GSTM1 eller Fc-gamma-RII genen samt för de som inte hade deletion av GSTT1 genen. Exponering för spannmålsdamm visade sig vara en signifikant större riskfaktor för RA för de som inte hade deletion av GSTM1, GSTT1 eller Fc-gamma-RII genen. Vidare visade individer som inte hade en deletion av Fc-gamma-RII genen en ökad risk för RA vid exponering för stendamm. / The aim of this study was to evaluate the effects of some environmental and genetic predisposing factors of Rheumatoid Arthritis (RA). RA is an inflammatory disease where the immune system decomposes body tissue. A significant increased risk of RA was shown when exposed to grain and smoking. The genes that were studied were GSTM1, GSTT1 and Fcgamma- RII. The genes themselves were no predisposing factors of RA, but smoking showed to be a significant greater riskfactor for RA for individuals having a deletion of the GSTM1 or the Fc-gamma-RII gene, or not having a deletion of the GSTT1 gene. Exposure to grain showed to be a significant greater riskfactor for RA for individuals not having a deletion of the GSTM1, GSTT1 or the Fc-gamma-RII gene. Also individuals not having a deletion of the Fc-gamma-RII gene showed an increased risk for RA when exposed to stonedust.

<p>IgG, IgM and IgE in complex with antigen have the capacity to regulate specific immune responses. In this investigation, the role of Fc receptors for IgG (FcγRI, FcγRII and FcγRIII) and complement receptors 1 and 2 (CR1/2) for antibody-mediated enhancement of antibody responses are investigated.</p><p>IgM is known to efficiently activate complement and thereby enhance specific antibody responses but it is not known if this involves binding to CR1/2. Using CR1/2 deficient mice, immunized with sheep erythrocytes alone or together with specific IgM, we present evidence that IgM-mediated enhancement is completely dependent on CR1/2 expression, whereas IgG or IgE in complex with bovine serum albumin (BSA) induce strong antibody responses in CR1/2-deficient mice. Enhancement by IgE is mediated via the low affinity receptor for IgE (FcεRII, CD23). However, the receptors which are involved in IgG-mediated enhancement are not known. We find that γ-chain-deficient mice (lacking FcγRI and FcγRIII) have impaired antibody responses to IgG/BSA complexes. In contrast, FcγRIII deficient mice have normal responses, suggesting that FcγRI mediates the effect. Furthermore, IgG/BSA complexes induce up to 189-fold stronger antibody responses in FcγRIIB-deficient mice than in wild-type mice. The threshold dose of IgG/BSA required was lower, the response was sustained for longer and initiated earlier in FcγRIIB-deficient than in wild-type animals. The findings suggest that FcγRIIB acts as a "safety-valve" preventing excessive antibody production during an immune response. We show for the first time that IgG3/BSA complexes can mediate enhancement of specific antibody responses. Their effect does not involve known Fcγ receptors.</p>

IgG, IgM and IgE in complex with antigen have the capacity to regulate specific immune responses. In this investigation, the role of Fc receptors for IgG (FcγRI, FcγRII and FcγRIII) and complement receptors 1 and 2 (CR1/2) for antibody-mediated enhancement of antibody responses are investigated. IgM is known to efficiently activate complement and thereby enhance specific antibody responses but it is not known if this involves binding to CR1/2. Using CR1/2 deficient mice, immunized with sheep erythrocytes alone or together with specific IgM, we present evidence that IgM-mediated enhancement is completely dependent on CR1/2 expression, whereas IgG or IgE in complex with bovine serum albumin (BSA) induce strong antibody responses in CR1/2-deficient mice. Enhancement by IgE is mediated via the low affinity receptor for IgE (FcεRII, CD23). However, the receptors which are involved in IgG-mediated enhancement are not known. We find that γ-chain-deficient mice (lacking FcγRI and FcγRIII) have impaired antibody responses to IgG/BSA complexes. In contrast, FcγRIII deficient mice have normal responses, suggesting that FcγRI mediates the effect. Furthermore, IgG/BSA complexes induce up to 189-fold stronger antibody responses in FcγRIIB-deficient mice than in wild-type mice. The threshold dose of IgG/BSA required was lower, the response was sustained for longer and initiated earlier in FcγRIIB-deficient than in wild-type animals. The findings suggest that FcγRIIB acts as a "safety-valve" preventing excessive antibody production during an immune response. We show for the first time that IgG3/BSA complexes can mediate enhancement of specific antibody responses. Their effect does not involve known Fcγ receptors.