Sjögren's syndrome (SS) and rheumatoid arthritis (RA) are characterised by breach of self-tolerance with high affinity circulating autoantibodies and peripheral B cell disturbances in the naïve and memory B cell compartments. In addition, both SS and RA develop functional ectopic B cell follicles in the respective target organs, i.e. the salivary glands and the joint synovium, whereby autoreactive B cell undergo antigen selection and affinity maturation. However, the exact stage at which errors in B cell tolerance checkpoints accumulate is unknown. In this PhD project, I amplified and sequenced Ig VH and VL gene transcripts from single B cells which were FACS sorted either from the peripheral blood of SS patients or from the RA synovium. Healthy donors (HD) were used as controls. Subsequently, I cloned and expressed recombinant monoclonal antibodies displaying identical antigenic specificity of the original B cells. Finally, I tested the poly- and autoreactivity profile of these antibodies against SS and RA-associated autoantigens. In SS, I analysed 353 VH and 293 VL sequences and obtained 114 recombinant antibodies from circulating naïve (n=66) and memory (n=48) B cells of 4 SS patients and compared their autoreactive and polyreactive profile to 45 naïve clones from 2 HD. Analysis of the VH and VL gene usage showed no significant differences between SS and HD. Conversely, I observed accumulation of circulating autoreactive naïve B cells in SS as demonstrated by Hep-2 cells, ENA, Ro/SSA and/or La/SSB reactivity. The elevated frequency of autoreactive naïve B cells in the circulation of SS patients supports the existence of early defects in B cell tolerance checkpoints in this condition In RA, I analysed the Ig gene repertoire and the VH gene somatic mutation rate of 139 VH and 175 VL sequences of synovial CD19+ B cells which demonstrated evidence of antigen selection and hypermutated alpha > gamma > mu VH chains with presence of intra-synovial clonal diversification. Recombinant antibodies from synovial B cell clones were then screened for reactivity towards citrullinated antigens with a plan for a wider analysis using autoantigen microarrays. Overall, these results highlighted the existence of B cell abnormalities and loss of tolerance for self-antigens both in the peripheral and/or lesional compartment of SS and RA. Further analysis of the fine specificity and pathogenicity of recombinant antibodies from autoreactive B cells will be invaluable in order to dissect the mechanisms and the antigens driving the development and the persistence of autoimmunity in RA and SS.

The book distills the available information on osteoporosis into an easily comprehensible format that serves as a practical guide for busy clinicians. Contents:Definition & epidemiology -- Basic bone pathophysiology -- Bone densitometry -- Diagnosis -- Identifying patients at risk of fractures -- Non-pharmacologic management of osteopenia and osteoporosis -- Pharmacologic management of osteoporosis, part 1 -- Pharmacologic management of osteoporosis, part 2 -- Monitoring patients on treatment -- Vertebral augmentation procedures -- Corticosteroid-induced bone loss -- Primary hyperparathyroidism -- Premenopausal women -- Men -- Atypical femoral shaft fractures -- Osteonecrosis of the jaw -- Osteoporosis in children and adolescents. / https://dc.etsu.edu/etsu_books/1077/thumbnail.jpg

<p><!-- @page { margin: 2cm } P { margin-bottom: 0.21cm; background: transparent; page-break-before: auto } P.western { font-size: 14pt } --></p><p>Rheumatoid arthritis is an autoimmune disease, where joints are attacked by the own immune system, leading to chronic inflammation and destruction of bone and cartilage. Inflammation is a complex process, controlled by many different substances. One of them is adenosine, which has anti-inflammatory properties. In this project, three polymorphisms in different genes, involved in synthesis and signaling of adenosine, were genotyped for 188 patients with RA and 362 controls without RA. The results shows that for the polymorphism in A2a, a gene coding for an adenosine receptor, there was no significant difference in genotype distribution between the groups. There were, however, some differences in the general sensation of pain and well-being reported by the patients. For the polymorphism in NT5E, a gene coding for a nucleotidase for extracellular adenosine synthesis, there were differences both regarding genotype distribution between the groups, and in the progression of the disease. The NT5E-AA genotype seems to increase inflammation, but decrease the number of tender joints. In the case of the polymorphism in ADA, which codes for adenosine deaminase, the minor allele frequency was too low for any conclusions to be made. An attempt was made to analyze the gene polymorphisms in relation to drinking habits, but the population was too small to generate any reliable conclusions. The project shows that the polymorphism in NT5E, whose functional consequences are yet unknown, might have an effect on the extracellular adenosin synthesis and RA pathogenesis. Further studies are required to shed more light on this matter.</p><p> </p> / <p>Reumatoid artrit är en autoimmun sjukdom där leder angrips av det egna immunförsvaret, vilket leder till kronisk inflammation och nedbrytning av brosk och ben. Inflammation är en komplex mekanism som regleras av många olika substanser, varav en är adenosin, som i förhöjda koncentrationer fungerar som en broms av inflammationen. I detta arbetet har tre olika polymorfier i gener inblandade i syntes och signalering av adenosin genotypats för 188 patienter med nydiagnostiserad RA, samt hos en kontrollgrupp på 362 frivilliga utan reumatisk sjukdom. Avseende en polymorfi i A2a, som kodar för en adenosinreceptor, fanns inga signifikanta skillnader i fördelning mellan fall och kontroller. Beträffande sjukdomsförloppet sågs dock vissa skillnader i patienternas bedömning av smärta och välbefinnande. För polymorfin i NT5E, som kodar för ett nukleotidas för extracellulär adenosinsyntes, hittades skillnader både i fördelningen mellan RA-gruppen och kontrollgruppen, samt i sjukdomsförloppet, där NT5E-AA genotypen var relaterad till högre inflammation, men samtidigt till lägre smärtupplevelse. För den tredje polymorfin (ADA) var antalet individer med mutant allel för litet för att tillåta några slutsatser. Tester gjordes även för att se om de olika adenosinpolymorfierna korrelerade till alkoholkonsumtion, men underlaget var för litet för att några slutsatser skulle kunna dras. Arbetet visar att polymorfin i NT5E, vars funktionella effekt är okänd, kan ha en effekt på nukleotidasets förmåga att producera extracellulärt adenosin. Kompletterande studier på större material behövs för att bringa klarhet i dessa frågor.</p>

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with systemic manifestations characterized by auto-antibodies directed against different parts of the cell nucleus including DNA, histones and ribosomes. The systemic inflammation can cause damage to multiple organs, e.g., kidneys, skin, heart, lungs and the nervous system. Rheumatoid arthritis (RA) is another autoimmune rheumatic disease characterized by auto-antibodies, mainly directed against the Fc-part of immunoglobulin G (rheumatoid factor (RF)) but also against citrullinated peptides/proteins (ACPAs). The inflammation in RA primarily involves the joints resulting in inflamed synovial tissue and destruction of cartilage. The aetiology of both SLE and RA is unclear but there is a genetic contribution predominantly of genes involved in inflammation. The diseases are believed to be multifactorial, or complex, meaning that multiple genes interact with environmental, infectious and hormonal factors, thus increasing the risk of developing disease. The aim of this study was to investigate different candidate genes involved in functions of the immune system and their relationship with SLE and RA susceptibility and severity. The patients and controls were from the four northernmost counties of Sweden, which is a fairly homogenous population well suited for genetic studies. Two single nucleotide polymorphisms (SNPs) in the oestrogen receptor α (ESR1) gene were analysed in SLE. No association was found between the SNPs and SLE per se however the minor alleles (PvuII C and XbaI G) were associated with skin manifestations and later disease onset, thus representing a milder form of the disease. A SNP in the programmed cell-death 1 (PDCD1) gene, which codes for PD-1, an inhibitory molecule involved in T-cell activation, was studied. No association was seen between the risk allele (PD-1.3A) and SLE susceptibility but a strong association was found with renal disease. A risk allele of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene that codes for a protein called Lyp which acts as a negative regulator of T-cell receptor (TCR) signalling was significantly associated with SLE in three different case-control sets across Sweden. Both PDCD1 and PTPN22 were independently associated with renal disease. The PTPN22 gene has been associated with numerous autoimmune diseases and was evaluated in another auto-antibody producing disease, RA. From the Medical Biobank of northern Sweden samples donated before the development of symptoms of RA were identified. In these individuals, who subsequently developed RA, the 1858T risk allele in combination with ACPAs gave a high relative risk (&gt;132) for developing RA. The association between PTPN22 and RA was confirmed in a larger material of patients with early RA. The 1858T allele, of the three SNPs investigated, was shown to be the true risk allele associated with auto-antibody positive RA. A functional role of PTPN22 in TCR-mediated activation of T cells from patients with SLE and RA was not demonstrated. In conclusion, minor alleles of two SNPs in the ESR1 gene were associated with a milder form of SLE. The risk allele in the PDCD1 gene was associated with renal disorder in SLE. The risk allele 1858T of the PTPN22 gene was associated with SLE, particularly with renal disease. The 1858T allele in combination with auto-antibodies was a risk factor for developing RA. In early diagnosed RA, the 1858T allele was highly associated with RA and in particular with auto-antibody positive RA.

La artritis reumatoide (AR) es la artropatía inflamatoria crónica más frecuente, afecta aproximadamente el 0.5% - 1% de la población general y causa una progresiva destrucción articular, discapacidad y disminución de la expectativa de vida. La etiología de la AR es desconocida y su patogenia solo parcialmente conocida al día de hoy. En los últimos años se han estudiado e identificado múltiples factores de riesgo para su desarrollo. Sabemos que intervienen factores genéticos y ambientales y que la interacción de ambos puede ser determinante en el desarrollo de la enfermedad. Entre los factores ambientales el tabaco ha sido ampliamente estudiado y actualmente se lo reconoce como el factor de riesgo no genético más importante para el desarrollo de AR, siendo este efecto particularmente importante en aquellos sujetos que presentan una susceptibilidad genética (presencia del epitopo reumatoide (ER)). Estudios más recientes ponen de manifiesto que el consumo de tabaco puede influir además en la expresión clínica de la enfermedad, determinar un curso evolutivo más grave y una mayor destrucción articular, aunque no todos los estudios son concordantes en estos últimos aspectos. El objetivo general de esta tesis fue analizar el efecto del consumo de tabaco en la expresión clínica y curso evolutivo de la artritis reumatoide en una cohorte de pacientes con artritis reumatoide de reciente comienzo. Para esto se llevó a cabo un estudio prospectivo en una cohorte de pacientes con artritis reumatoide de inicio (menos de dos años desde el inicio de los síntomas). En ellos se analizaron las características epidemiológicas, clínicas, serológicas y radiológicas basales y periódicamente, cada tres meses, hasta los dos años de evolución. Estas variables fueron comparadas entre aquellos pacientes fumadores y los no fumadores. Se observó que los pacientes con AR fumadores son con mayor frecuencia son portadores del epitopo reumatoide, lo que sugiere la existencia de una relación genético-ambiental en el desarrollo de la AR. En nuestra serie no hemos podido observar relación entre el consumo de tabaco y la presencia de ACPA. Desde el punto de vista de la expresión clínica de la AR, los pacientes fumadores presentaron un debut de su enfermedad más temprano que los no fumadores. La actividad clínica y biológica de la enfermedad y discapacidad que presentaron tanto al momento del debut de la AR como tras dos años de seguimiento fueron similares entre fumadores y no fumadores. El tabaco no parece influir en la expresión clínica de la enfermedad (a corto plazo). En cuanto a la destrucción articular, el tabaco demostró ser un factor predictor independiente de destrucción articular, junto con el sexo femenino y la presencia del ER. No obstante la magnitud de este efecto sería moderada. La prevalencia de ACPA en la población sana, tanto si son fumadores o no lo son, es del 1.9%. En grandes fumadores el consumo de tabaco no determina una mayor producción de ACPA. Sin embargo los grandes fumadores con EPOC sí tendrían una mayor predisposición a la producción de ACPA, aunque a títulos bajos. La implicación y relevancia clínica de los mismos debe ser aún estudiada en mayor profundidad.

Rheumatoid arthritis is an autoimmune disease, where joints are attacked by the own immune system, leading to chronic inflammation and destruction of bone and cartilage. Inflammation is a complex process, controlled by many different substances. One of them is adenosine, which has anti-inflammatory properties. In this project, three polymorphisms in different genes, involved in synthesis and signaling of adenosine, were genotyped for 188 patients with RA and 362 controls without RA. The results shows that for the polymorphism in A2a, a gene coding for an adenosine receptor, there was no significant difference in genotype distribution between the groups. There were, however, some differences in the general sensation of pain and well-being reported by the patients. For the polymorphism in NT5E, a gene coding for a nucleotidase for extracellular adenosine synthesis, there were differences both regarding genotype distribution between the groups, and in the progression of the disease. The NT5E-AA genotype seems to increase inflammation, but decrease the number of tender joints. In the case of the polymorphism in ADA, which codes for adenosine deaminase, the minor allele frequency was too low for any conclusions to be made. An attempt was made to analyze the gene polymorphisms in relation to drinking habits, but the population was too small to generate any reliable conclusions. The project shows that the polymorphism in NT5E, whose functional consequences are yet unknown, might have an effect on the extracellular adenosin synthesis and RA pathogenesis. Further studies are required to shed more light on this matter. / Reumatoid artrit är en autoimmun sjukdom där leder angrips av det egna immunförsvaret, vilket leder till kronisk inflammation och nedbrytning av brosk och ben. Inflammation är en komplex mekanism som regleras av många olika substanser, varav en är adenosin, som i förhöjda koncentrationer fungerar som en broms av inflammationen. I detta arbetet har tre olika polymorfier i gener inblandade i syntes och signalering av adenosin genotypats för 188 patienter med nydiagnostiserad RA, samt hos en kontrollgrupp på 362 frivilliga utan reumatisk sjukdom. Avseende en polymorfi i A2a, som kodar för en adenosinreceptor, fanns inga signifikanta skillnader i fördelning mellan fall och kontroller. Beträffande sjukdomsförloppet sågs dock vissa skillnader i patienternas bedömning av smärta och välbefinnande. För polymorfin i NT5E, som kodar för ett nukleotidas för extracellulär adenosinsyntes, hittades skillnader både i fördelningen mellan RA-gruppen och kontrollgruppen, samt i sjukdomsförloppet, där NT5E-AA genotypen var relaterad till högre inflammation, men samtidigt till lägre smärtupplevelse. För den tredje polymorfin (ADA) var antalet individer med mutant allel för litet för att tillåta några slutsatser. Tester gjordes även för att se om de olika adenosinpolymorfierna korrelerade till alkoholkonsumtion, men underlaget var för litet för att några slutsatser skulle kunna dras. Arbetet visar att polymorfin i NT5E, vars funktionella effekt är okänd, kan ha en effekt på nukleotidasets förmåga att producera extracellulärt adenosin. Kompletterande studier på större material behövs för att bringa klarhet i dessa frågor.

Rheumatoid arthritis (RA) is a progressive disease, often leading to disability. Because the disease course develops rapidly during the first years after diagnosis, more knowledge is needed about the early disease course to minimize later disability. This thesis describes the course of disability in early RA such as hand function, pain intensity, activity limitation and sick leave. In addition, this thesis compares disability between women and men and compares disability between RA patients and referents. This thesis is primarily based on data from the 320 patients that were included in the multi-centre project in Sweden called ‘Early interventions in rheumatoid arthritis’ (TIRA). A wide range of outcome variables was registered between 1996 and 2006 during regular follow-ups from time for diagnosis through the eight-year follow-up. Outcome regarding disease activity and disability of RA patients still remaining in TIRA at the three and five year follow-up respectively are used in this thesis. Data concerning sick leave were obtained for the patients during six years (1993-2001) – three years before and three years after diagnosis. Referents were included in two of the studies. Data regarding disability in referents were obtained according to hand function and activity limitation using the Health Assessment Questionnaire (HAQ). Data for sick leave were obtained for six years in referents, for the same period as the RA patients. For most variables, disability in RA was most pronounced at time of diagnosis but before intervention started. Disability was then reduced already at the 3-month follow-up and thereafter affected but stable during the following five years. The exception was participation, reflected by sick leave, a variable that was stable from inclusion to three years from diagnosis. Activity limitation, pain intensity and sick leave in RA that represents different aspects of disability were explained by other aspects of disability and contextual factors rather than by disease activity. RA affects women and men differently in some aspects. Women had more severe course of activity limitations than men according to HAQ. Men were more affected than women in range of motion, although the differences were small in a clinical perspective. However, pain intensity and frequency of sick leave did not differ between women and men. Patients with RA have pronounced disability in relation to referents although several variables improve soon after diagnosis. This discrepancy refers to hand function as well as activity limitations and sick leave. The frequency of sick leave increased during the year before diagnosis in relation to referents and was thereafter high compared to sick leave in referents.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of a wide range of autoantibodies, multiple organ involvement and by local formation or tissue deposition of immune complexes (ICs) in the inflamed organs. In contrast to most systemic inflammatory conditions, and despite raised levels of pro-inflammatory cytokines, SLE flares are rarely reflected by elevated C-reactive protein (CRP), an important acute-phase reactant in man with homologs in vertebrates and several invertebrates. As a part of the innate immune system, CRP binds certain molecules exposed on the surface of dying cells/apoptotic bodies and on the surface of pathogens and mediates their elimination by uptake in the reticuloendothelial system. CRP also interacts with IgG-containing immune complexes, binds Fc receptors and activates the complement system via C1q. The aims of this thesis were to investigate the complement activation properties of CRP; to elucidate if anti-CRP antibodies occur in SLE and, if so, whether anti-CRP antibody levels correlate with disease activity in SLE; to test the hypothesis that autoantibodies to pro-inflammatory cytokines prevent rise of CRP; and to survey if autoantibodies to certain nuclear antigens or to CRP correlate with cytokine-inducing properties of ICs from SLE sera. We have demonstrated that CRP bound to phosphorylcholine is a powerful activator of the classical complement pathway already in the CRP concentration range 4 to 10 mg/L, but with a marked inhibition at CRP levels above 150 mg/L. Autoantibodies to the monomeric form of CRP were found in approximately 40 percent of SLE patients and in a few sera from patients with primary Sjögren’s syndrome, but not in rheumatoid arthritis or in inflammatory bowel disease. The anti-CRP antibody levels showed significant correlations to several laboratory and clinical measurements, and anti-CRP positivity was associated with renal involvement in SLE. Native CRP levels were not correlated with anti-CRP or anti-cytokine antibody levels. Hence, the presence of antibodies to monomeric CRP or to CRP-inducing cytokines is an unlikely explanation to the relative failure of CRP response in patients with active lupus. However, antibodies to TNFα were found in subnormal levels at disease flares, whereas antibodies to TGFβ were found in supranormal levels as compared to healthy subjects. In contrast to antibodies against CRP and DNA, anti-SSA and anti-SSB antibodies may regulate the inflammatory process in SLE by enhancing IC formation and subsequent production of cytokines such as IL-6, IL-10 and IL-12p40. Hypothetically, anti-CRP autoantibodies may be of pathogenic importance, for instance by binding to monomeric CRP on cell and tissue surfaces and thereby increasing the risk of extrahepatic deposition of apoptotic material and in situ formation of ICs. / On the day of the defence data the status of article I was Submitted and the tile was "C-reactive protein activates or inhibits the classical complement pathway in a concentration dependent manner" and the status of article V was: Submitted.

Rheumatoid arthritis (RA) is a major cause of progressive joint damage and disability, and is associated with decline in quality of life, reduced ability to work and increased health care utilisation. The economic consequences of the disease are substantial for the individuals and their families and for the society as a whole. This thesis describes a 5-year follow up of 320 patients with early RA, enrolled between January 1996 and April 1998 in the Swedish multi-centre inception cohort TIRA (early interventions in rheumatoid arthritis). Health status, function and costs were investigated. Predictors of high costs were calculated, and an algorithm was constructed to predict future need for TNFinhibitor treatment in patients not responding to traditional disease-modifying antirheumatic drugs (DMARDs). Clinical and laboratory data, measures of functional capacity and self-reported assessments were collected regularly. In addition, patients completed biannual/annual questionnaires concerning all health care utilisation and days lost from work due to the disease. Within 3 months, improvements were seen regarding all variables assessing disease activity and functional ability, but 15% of the patients had sustained high or moderate disease activity throughout the study period. The scores of ‘health assessment questionnaire’ (HAQ) were similar for men and women at baseline, but had a less favourable course in women, who also had DMARDs more frequently prescribed. Ambulatory care accounted for 76% of the direct costs during the first year. Women had more ambulatory care visits and higher usage of complementary medicine compared to men. Men ≥65 years had low costs compared to younger men and compared to women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM-class rheumatoid factor (RF), and poor hand function increased the odds of incurring high direct costs. Poor hand function and pain increased the odds of incurring high indirect costs. Indirect costs exceeded direct costs all three years. The average direct costs were €3,704 (US$ 3,297) year 1 and €2,652 (US$ 2,360) year 3. All costs decreased over the years, except those for medication and surgery. The indirect costs were €8,871 (US$ 7,895) year 1 and remained essentially unchanged, similarly for both sexes. More than 50% were on sick leave or early retirement at inclusion. Sick leave decreased but was offset by increase in early retirement. 14 patients (5%) were prescribed TNF-inhibitors at the 3- year follow up, thus increasing drug costs substantially. However, they incurred higher costs even before prescription of anti-TNF therapy. At the 5-year follow-up (2001-2003), 31 patients (12%) were prescribed TNFinhibitors. Baseline values of erythrocyte sedimentation rate, C-reactive protein, anti-CCP antibodies and morning stiffness were significantly higher in this group. These patients were also to a larger extent RF-positive and carriers of the ‘shared epitope’ (SE). Anti-TNF treated patients were significantly younger and more often women. For men, a predictive model was constructed using baseline data including SE+ and IgA-RF &gt;100 U/L and anti-CCP &gt;240 U/L yielding a specificity of 98% and a sensitivity of 71%. For women, disease activity score (DAS28) at the 3-month follow-up proved to be a better predictor, and the final model comprised SE+ and 3-month DAS28&gt;5.2, giving a specificity of 95% and a sensitivity of 59%.

Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration. Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE. Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR. Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody. In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders. Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.