PubMed · 12585991
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Richard P Usatine. 2003. Abnormal fingernails.. https://pubmed.ncbi.nlm.nih.gov/12585991/
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OBJECTIVE: To analyze S-100 protein expression, in the form of myeloid-related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients. METHODS: Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme-linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry. RESULTS: MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean +/- SD 15310 +/- 16999 ng/ml [median 11400]) than in serum (908 +/- 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C-reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute-phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores. CONCLUSION: MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis.
Etanercept, a competitive inhibitor of TNF-alpha, is currently FDA approved for psoriatic arthritis and rheumatoid arthritis. The molecular structure of etanercept, its mechanism of action, and results of clinical trials involving patients with psoriasis will be reviewed.
Psoriatic arthritis (PsA) is an inflammatory arthritis that may affect as many as 30% of patients with psoriasis (Ps). Genetic factors play an important role in the susceptibility to and the expression of PsA. The objective of this study was to identify whether haplotype sharing among affected sibling pairs of individuals with PsA is increased compared with unaffected sibling pairs. We collected 182 sibling pairs of probands affected with PsA. Extracted genomic DNA was amplified in polymerase chain reactions using locus specific primers homologous to nucleotide sequences for each of the HLA-A, -B, -C, -DR, and -DQ loci. Polymerase chain reaction amplicons were identified by reverse line blot assay using sequence-specific oligonucleotide probes. Evidence for excessive haplotype sharing was examined through Green and Woodrow's test. Results indicate that of the 182 sibling pairs, 46 were affected by PsA, 48 by Ps, and 88 were unaffected. The sharing of 2, 1, and 0 haplotypes for the PsA affected sibling pairs was 14, 27, and 5, respectively (p = 0.04); whereas the haplotype sharing for the Ps affected sibling pairs was 12, 26, and 10, respectively (p = 0.38). In conclusion, the human leukocyte antigen region on chromosome 6p is implicated as one of the candidate regions in PsA.