S. Rantapää Dahlqvist

Antibodies against cyclic citrullinated peptide (CCP) in psoriatic patients with or without joint inflammation

Objective: To compare the prevalence of anti-CCP antibodies in psoriatic patients with and without joint inflammation, patients with early RA, and controls. Methods: Anti-CCP antibodies (cut off level 5 U/ml) were measured in 160 patients with psoriatic arthritis (PsA), 146 patients with psoriasis but no arthritic disease, 101 patients with early RA, and 102 healthy controls by ELISA. Results: 11 (7%) patients with PsA, 75 (74%) patients with early RA, 2 (2%) healthy controls (2%), and 1 (0.7%) patient with psoriasis without arthritis had anti-CCP antibodies above the cut off level. The presence of anti-CCP antibodies was not related to radiological changes and/or deformity and functional impairment in PsA. 8/11 patients with PsA and anti-CCP antibodies had a polyarthritic disease, and all fulfilled the ACR criteria for RA at 4 year follow up. Five of these 8 patients also had manifestations such as dactylitis, DIP involvement, radiological changes associated with PsA, and/or enthesitis. In multiple logistic regression analysis with polyarthritis as the dependent variable, anti-CCP antibodies and rheumatoid factor significantly distinguished RA from PsA. Conclusions: Anti-CCP antibodies were more prevalent in patients with PsA than in patients with psoriasis without arthritis, but less prevalent than in patients with early RA. Patients with PsA positive for anti-CCP antibodies more often had polyarthritic disease, but the presence of anti-CCP antibodies did not relate to radiological changes and/or deformity and functional impairment.

Conversion towards an atherogenic lipid profile in rheumatoid arthritis patients during long‐term infliximab therapy

Objectives: To analyse the effects of infliximab infusions on serum levels of lipids in patients with rheumatoid arthritis (RA) treated for 2 years. Methods: Fifty‐two patients (41 females and 11 males) with RA undergoing infliximab treatment (3 mg/kg) were consecutively recruited into the study. The mean (±SD) age of the patients was 54.6±12.5 years and mean disease duration was 14.1±8.6 years. Blood was sampled before infusion at baseline, and at 3, 6, 12, 18 and 24 months. Forty‐one of the patients were also treated with methotrexate, 13 with other disease‐modifying anti‐rheumatic drugs (DMARDs) and 28 with prednisolone (<10 mg daily). For comparison, lipid levels were followed for 2 years in 70 consecutively included patients with early RA during treatment with conventional DMARDs. Results: There was an initial increase in plasma levels of cholesterol, high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, and LDL/HDL and total/HDL cholesterol ratios. However, after 3 months HDL‐cholesterol decreased significantly, followed after 6 months by cholesterol and LDL‐cholesterol. The LDL/HDL and total/HDL‐cholesterol ratios remained significantly raised. HDL‐cholesterol increased and the ratios improved in patients with early RA receiving conventional treatment. The changes over time differed significantly between the patient groups. Conclusion: During infliximab infusion a pro‐atherogenic lipid profile developed despite reduced inflammatory activity. The long‐term decrease in HDL‐cholesterol was unexpected considering the known effects of tumour necrosis factor‐alpha (TNFα).

Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden

Abstract: The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.

Thrombocytosis in active rheumatoid arthritis. Relation to other parameters of inflammatory activity and confounding effect of automated cell counting

SummaryThe magnitude of thrombocytosis and the possible confounding effect of platelet clumping, an in vitro artifact resulting in spuriously low platelet counts, in active rheumatoid arthritis (RA) was evaluated by a prospective survey of 57 consecutive patients, 60% of whom had thrombocytosis. Five cases (9%) of platelet clumping, assessed by H6000 pictures, were found. A low-grade platelet loss in may of the samples anticoagulated by EDTA was suggested by comparison with platelet counts obtained in parallel blood samples anticoagulated by citrate. Thus, the possibility of spuriously low platelet counts due to laboratory artifacts must always be taken into consideration in RA patients. The relation between thrombocytosis and other estimates of disease activity was also studied. The platelet count in citrated blood in active RA was significantly correlated with ESR, acute phase plasma proteins, and neutrophil, basophil and monocyte counts. In a multivariate regression model, however, only the correlation with haptoglobin (p=0.06) approached significance.

Bf and C3 Complement Types in Rheumatoid Arthritis

Bf and C3 complement types were studied in 100 male and 100 females patients from northern Sweden with erosive rheumatoid arthritis (RA) and compared with population controls. A significantly decreased frequency of the Bf FS phenotype was found particularly in males and in patients with a family history of polyarthritis. Significant Bf associations were also found with a more severe form of RA (functional classes III and IV) and with high titers of the rheumatoid factor. No significant difference with respect to C3 phenotype and gene frequencies was found between RA patients and controls. Thus, the association between RA and C3F found in some previous investigations was not confirmed.

Acetylator Phenotypes in Rheumatoid Arthritis Patients with or without Adverse Drug Reactions to Sodium-Aurothiomalate or d-Penicillamine

The acetylator phenotype was determined in 59 patients with classical, seropositive and erosive rheumatoid arthritis (RA) treated with sodium-aurothiomalate or d-penicillamine. Patients with adverse drug reactions (ADR) leading to drug withdrawal (n = 29) were compared with a group of patients without ADR (n = 30). The frequency of slow acetylators was significantly (p less than 0.05) increased in all RA patients, irrespective of the presence of ADR, particularly in the male patients, compared with a control population. No association was found between acetylator phenotype and clinical data or secondary Sjögrenss syndrome (SS).

HLA antigens and adverse drug reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis

SummaryThe association between HLA antigens and adverse drug reactions (ADR), (e.g. proteinuria, haematological abnormalities, stomatitis, diarrhoea and dermatitis) in rheumatoid arthritis (RA) to sodium aurothiomalate (gold) and to Dpenicillamine (PA) were studied in 32 patients. Thirtyeight RA patients treated with gold and PA, and with no ADR to these drugs, were used as controls. The frequency of HLA B8 was significantly (p<0.05) increased among RA patients with ADR compared to plasma donors. DR3 was also significantly increased (p<0.05) in RA patients with haematological ADR compared to plasma donors. Haematological ADR occured significantly (p<0.05) more often in DR3 positive patients (55%) than among DR3 negative RA patients (27%).

Transferrin C Subtypes and Rheumatoid Arthritis

Transferrin C subtypes were studied in patients with rheumatoid arthritis (RA) and controls. A significant association was found between the C2 type and RA. This association concerned mainly male patients and patients with a family history of polyarthritis. The results were discussed in relation to previous studies of the role of oxygen free radicals in the pathogenesis of RA and to a recently proposed hypothesis that the TfC2 gene confers an increased risk for cellular damage by hydroxyl radicals.

Alpha-1-antitrypsin types and rheumatoid arthritis

Frequencies of alpha‐1‐antitrypsin (Pi) phenotypes were studied in 100 female and 100 male Swedish patients with classical rheumatoid arthritis and compared with the population frequencies. A significant increase of rare Pi types (MS, MZ, MF and SZ) was found among the patients. However, the increase concerned mainly Z heterozygotes and was more strongly pronounced in male patients. The M‐subtypes showed no association with rheumatoid arthritis. Previous investigations of Pi types in rheumatoid arthritis have shown somewhat variable results. The results so far indicate, however, that an association between the Z allele and rheumatoid arthritis is likely to exist, while the evidence for a relationship between rheumatoid arthritis and other Pi alleles is considerably weaker.

Chromosomal changes in rheumatoid arthritis patients treated with CPH82

SummaryChromosomal changes were assessed in 19 patients with rheumatoid arthritis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside, for up to one year. The frequency of chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in peripheral lymphocytes increased significantly after 12 weeks of treatment and remained elevated after 48 weeks treatment in peripheral lymphocytes. The number of CA and SCE were significantly increased in CPH82 treated patients compared with the RA patients treated with other disease modifying anti-rheumatic drugs (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexate, cyclophosphamide). Only two patients treated with cyclophosphamide and azathioprine had changes of comparable levels. The results of this study suggest a mutagenic potential of CPH82 similar to that described for other immunosuppressive drugs and the newer podophyllotoxin derivatives, etoposide and teniposide.