Objectives: Anti-citrullinated peptide antibodies (ACPAs) are established as useful predictors of radiographic progression in rheumatoid arthritis (RA). The main objective of this study was to test the prognostic capacity of the recently developed test for anti-mutated citrullinated vimentin (anti-MCV).Methods: A cohort of 238 patients with RA was followed longitudinally for 10 years; 125 patients with complete x ray sets were included in the main analyses. Radiographs were scored according to the van der Heijde modified Sharp score (SHS). Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 "shared epitope'' (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T.Results: Anti-MCV and anti-CCP were strongly associated with regard to status and level. Both antibodies were associated with SE, but only anti-MCV was significantly associated with PTPN22 1858T. A positive anti-MCV test increased the odds of radiographic progression by 7.3 (95% confidence interval (CI) 3.2 to 16.5) compared to 5.7 (95% CI 2.6 to 12.5) for a positive anti-CCP. Presence of MCV antibodies gave an average increase in the total SHS of 30 U compared to an average increase of 25 U for the presence of CCP antibodies. Anti-MCVs were more strongly associated to progression in erosions than joint space narrowing. Associations remained after adjustment for other predictors of radiographic progression. The odds of progression increased with increasing anti-MCV level.Conclusions: Presence of anti-MCV predicted joint damage, and the strength of this prediction was at least as strong as for anti-CCP. Antibody status showed a stronger association to bone than to cartilage destruction. This study also indicates that higher anti-MCV levels add prognostic information compared to their mere presence or absence.

A patient, O.A., had in her serum an IgM rheumatoid factor (RF) of high titer which reacted equally well with monomeric and polymeric rabbit IgG, but showed no reaction with homologous or autologous monomeric and polymeric IgG, neither in hemagglutination nor in ELISA tests. In contrast to the usual specificity of RFs crossreacting with rabbit and human IgG, which require the presence of both the CH2 end CH3 domains, the O.A. RF showed reaction only against the CH3 domain. The existence of human RF not reacting with human IgG could challenge the notion that RF production is necessarily induced by autologous IgG and thus playing an important role in potentiating and regulating secondary immune responses. The O.A. RF might represent 1: an extreme case of heteroclitic antibody, 2: the internal image of a hypothetical Fc-receptor reacting with rabbit IgG but not with human IgG, 3: a result of polyclonal B cell activation, 4: an antigenic crossreaction with an unknown antigen with similarities to rabbit IgG but not to human IgG.

OBJECTIVES:New effective therapies with particularly good effect on joint destruction have highlighted the need for reliable predictors of radiographic progression in rheumatoid arthritis (RA). Our objective was to assess the combined predictive role of a set of laboratory markers with regard to 10-year radiographic progression, and to examine the effect of anti-cyclic citrullinated peptide (anti-CCP) level.METHODS:A cohort of 238 patients with RA was followed longitudinally for 10 years with the collection of clinical data and serum samples. 125 patients with radiographs of the hands available at both baseline and after 10 years were included in this study. Radiographs were scored according to the van der Heijde modified Sharp score. Baseline sera were analysed for C-reactive protein, erythrocyte sedimentation rate (ESR), anti-CCP, IgA rheumatoid factor (RF) and IgM RF. Logistic regression analyses were used to identify predictors of radiographic progression and to examine the effect of anti-CCP level.RESULTS:Anti-CCP (OR 4.0; 95% CI 1.6 to 10.0) was the strongest independent predictor of radiographic progression. Female gender (OR 3.3; 95% CI 1.3 to 7.6), high ESR (OR 3.2; 95% CI 1.2 to 7.6) and a positive IgM RF (OR 3.1; 95% CI 1.2 to 7.9) were also independent predictors. Compared with the anti-CCP-negative patients, patients with low to moderate levels of anti-CCP (OR 2.6; 95% CI 0.9 to 7.2) and patients with high levels of anti-CCP (OR 9.9; 95% CI 2.7 to 36.7) were more likely to develop radiographic progression.CONCLUSIONS:Anti-CCP, IgM RF, ESR and female gender were independent predictors of radiographic progression and could be combined into an algorithm for better prediction. Patients with high levels of anti-CCP were especially prone to radiographic progression, indicating that the anti-CCP level may add prognostic information.

Despite the effects of BCR ABL on cell proliferation, no study has compared the proliferative rate of different haematopoietic cell compartments from chronic myeloid leukaemia (CML) with those of normal bone marrow (NBM). We comparatively analysed the cell cycle distribution and BCR/ABL expression in different compartments of BM cells from 15 CML and 11 NBM. Overall, our results showed similar proliferative indices in CML patients and NBM. However, CD34+ myeloid precursors from CML patients displayed an increased proportion of S + G2/M-phase cells (P = 0.04), while no significant differences were found between CML and NBM for other BM cell subsets analysed. In BM cells separated by fluorescence-activated cell sorting, decreasing levels of BCR/ABL mRNA were found from CD34+/CD38+ myeloid precursors to myeloblasts; BCR/ABL expression increased afterwards with a peak at the myelocyte/metamyelocyte stage, decreasing in the more mature band/neutrophil compartment. Unexpectedly, BCR/ABL gene expression showed an inverse correlation with the proportion of S + G2/M-phase cells (R = -0.33; P = 0.04). These results suggest that in CML, BCR/ABL expression is associated with an increased proliferation of CD34+ myeloid haematopoietic progenitor cells but not of other more mature myeloid precursors, as confirmed by the observation of an inverse correlation between the amount of BCR/ABL transcripts and the proportion of S + G2/M-phase cells.

Objectives The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy.Methods We performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test.Results There was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles.Conclusions Our study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.

The scarce data published on mite sensitization and mite‐allergen levels in Norway indicate that the mites may not be of the same importance in allergic disease in Norway as in countries such as the UK and the rest of Europe. The problem also involves the low allergen levels and small amounts of dust collected for allergen determination, and when the level is to be expressed as mg/g, the lower detection limit will often vary from sample to sample, giving within the same investigation results such as < 0.2 μg/g, < 0.5 μg/g, and even <2.0 μg/g. The use of allergen levels expressed instead per area (μg/m2) at least results in a uniform lower detection limit, making statistical analysis easier.

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are liphophilic compounds markedly resistant to biological degradation. They persist for a long time in nature and can accumulate within the food chain (Fletcher and McKay 1993). Humans, for example, fishermen consuming contaminated fish and other seafood from polluted lakes and seas, may therefore be exposed to substantially elevated levels of these compounds (Humphrey 1987, Svensson et al. 1991).

The subclass distribution of IgG-producing immunocytes was studied by two colour immunohistochemistry with monoclonal antibodies in jejunal biopsy specimens from 10 adults with untreated coeliac disease, 11 coeliac disease patients on a gluten free diet, and seven patients with established food allergy. Paired immunofluorescence staining was performed with subclass specific murine monoclonal antibodies in combination with polyclonal rabbit antibody reagent to total IgG; the proportion of cells belonging to each subclass could thereby be determined. The ratio of IgG2 immunocytes was significantly higher (p less than 0.05) in untreated coeliac disease patients (median, 35.2%; range, 26.7-65.2%) than in those on a gluten free diet (median, 7.3%; range, 0-31.9%) or those having food allergy (median, 12.5%; range, 0-36.5%). The disparity in the local IgG2 response between patients with untreated coeliac disease and those with food allergy might be due to differences in the nature of the antigenic stimuli, dissimilar genetic 'make-up' of the subjects, or both.

The prevalence of thyroid dysfunction and thyroid antibodies was investigated in a small rural community (Naerøy) and in Oslo. Attendance rates in Naerøy and Oslo were 99 and 71%, respectively. The prevalence of undiagnosed latent hypothyroidism and primary hypothyroidism was 4.0 and 5.3% in women in Oslo and Naerøy respectively and 0 and 3.5% in men. Undiagnosed hyperthyroidism was detected in 1.2% of men in Naerøy and in 1% of women in Oslo. Antibody to the thyroid microsomal antigen in titre greater than or equal to 400 was detected in 10.2 and 17.5% of women and 7.3 and 7.2% of men in Oslo and Naerøy, respectively. Among women with antibody to the thyroid microsomal antigen in both Oslo and Naerøy, and among men in Naerøy, the prevalence of past or present thyroid dysfunction was increased.

The prevalence of thyroid dysfunction was investigated in a small, rural community located at the coast in Middle Norway. Two hundred persons (114 women and 86 men) of the total 802 persons over 70 years of age in the community were examined regarding thyroid dysfunction. Blood samples were drawn from 197 (113 women and 84 men). In women previously diagnosed hypothyroidism was found in 3.5% and previously diagnosed hyperthyroidism in 0.9%. In men no previously diagnosed thyroid disease was found. Undiagnosed primary hypothyroidism (TT4 less than 70 nmol/l and TSH greater than 6 mU/l) was found in 1.8% and 1.2% of women and men, respectively. Latent hypothyroidism (TT4 70-150 nmol/l and TSH greater than 6 mU/l) was found in 3.5% and 2.4%, and borderline hypothyroidism (TSH 4.5-6.0 mU/l) in 3.5% and 2.4%, respectively. Undiagnosed hyperthyroidism was not found in women but in 1.2% of men. Antibody to the thyroid microsomal antigen (TMA) greater than or equal to 400 was detected in 17.5% of women and 9.6% of men. Clearly elevated serum thyrotropin (TSH) concentrations or previously diagnosed thyroid disease were found in 21.7% and 37.5% of the TMA positive women and men, respectively.

A comparison between 70 patients with ankylosing spondylitis and 97 controls revealed no significant differences in Gm allotypes. In the patients, no association was found between Gm types and various clinical features.

A 13 year old girl with the typical clinical and haematological picture of congenital dyserythropoietic anaemia (CDA) is reported. The bone marrow is highly cellular with 70 per cent erythroid cells, and 28% bi- and multinuclear cells among the orthochromatic and polychromatic erythroblasts. Moderate megaloblastoid changes are present. On light microscopy the findings are in agreement with those described in CDA type II. On electron microscopy both the cytoplasmatic changes described as typical of CDA type II, and the nuclear changes found in type I can be demonstrated. The acidified serum test (Ham test) is negative with normal sera. The patient's red blood cells show increased agglutinability with anti-I and and anti-I antibodies, but no haemolysis. Total serum lipids are about 50% of the normal average. All lipoprotein classes are lowered to about the same extent. The total phospholipid content of the erythrocytes is slightly reduced, with a moderate, relative increase of the lecithin fraction and a decrease of the sphingomyelin fraction. Doubts can be raised about the tenability of the current classification of CDA based on morphological and serological criteria, especially about the distinction between types I and II.

A hidden rheumatoid factor, reacting with a human IgG antigen, called “non b”, present on all Gm(b) negative IgG3 proteins, and also on all IgG1 and IgG2 proteins, but not on IgG3 Gm(b) or IgG4, was revealed by gel filtration. A similar specificity was demonstrated in two properly absorbed baboon antisera against human myeloma proteins. The “non b” antigen could be further divided into “non b1,” detected by the rheumatoid anti-“non b” and by one of the baboon antisera, and “non b0” detected by the other hetero-antiserum. The “non b0” antigen was present on the pFc′ and Fc′ fragments of human IgG, whereas “non b1” was found to be present on Fc outside pFc. This subdivision of “non b” was further supported by experiments with selected IgG3 myeloma proteins and anti-Rh antibodies.′ The “non b0” and “non b1” antigens reflect the close relationship among the IgG subclass proteins and may be valuable markers in studying the evolution of the IgG subclasses.