Lessons learned from clinical phenotypes in early psoriatic arthritis: the real-world Dutch south west Early Psoriatic ARthritis study.

Objective: This paper describes the baseline demographics, clinical characteristics, and patient-reported outcomes (PROs) according to clinical phenotype of patients with early psoriatic arthritis (PsA) for the purpose of creating a decision support system for daily clinical practice.Method: Patients with newly diagnosed PsA were included in the Dutch south west Early Psoriatic ARthritis (DEPAR) study. No classification criteria were applied, to ensure collection of real-world data on demographics, medication, clinical characteristics, and PROs. An IT infrastructure facilitated data collection.Results: We described 527 patients, categorized according to the clinical phenotype stated by the rheumatologist at the time of diagnosis, namely monoarthritis (15%), oligoarthritis (40%), polyarthritis (23%), enthesitis (10%), axial disease (2%), and dactylitis (10%). Overall psoriasis severity was mild and 83 patients (16%) had no psoriasis. Short-term sick leave (> 1 day per 4 weeks) was 17% and long-term sick leave (> 4 weeks) was 4%. The group with phenotype enthesitis reported the longest duration of complaints, had the highest fatigue scores, and contained the highest percentage of patients with a Hospital Anxiety and Depression Scale (HADS) anxiety score ≥ 8 and depression score ≥ 8.Conclusion: PsA patients presenting at outpatient clinics in the Netherlands had a mild degree of psoriasis, with impairment of quality of life and work productivity. Most patients presented with phenotype oligoarthritis. Those presenting with phenotype enthesitis more often reported scores suggestive of an anxiety or depression disorder and fatigue. It is important for attending rheumatologists to be aware of these differences when assessing patients with PsA.

Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease.

OBJECTIVE: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). BACKGROUND: MS is an immune-mediated disease and cytokines hove been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. METHODS: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T MS patients express significantly more CD4+ and CD8+ T cells were analyzed for IFN-gamma, IL-2, TNF-alpha, IL-4, IL-10 and IL-13 production. RESULTS: cells producing IFN-gamma compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-alpha and a significant increase in CD8+ T cells producing IL-4 and IL-10. CONCLUSIONS: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.

Treatment with monoclonal anti-tumor necrosis factor alpha antibody results in an accumulation of Th1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: In rheumatoid arthritis (RA), treatment with tumor necrosis factor alpha (TNFalpha) binding agents has proven to be highly effective. Downregulation of the proinflammatory cytokine cascade and a reduced migration of leukocytes into the joints have been proposed as modes of action of TNFalpha blockade. We investigated whether alterations in the number of circulating pro- and antiinflammatory T cell subsets contribute to the therapeutic effect of monoclonal antibodies (mAb) against TNFalpha in RA patients. METHODS: Phenotypic analysis of peripheral blood T cell subsets was performed on blood from RA patients before and after treatment with an anti-TNFalpha mAb. RESULTS: An accumulation of primed CD45RA- T cells of both the CD4+ and the CD8+ T cell population was seen shortly after treatment. Most notably, within the CD4+,CD45RA- T cell subset, the number of interferon-gamma-producing T cells was significantly increased after anti-TNFalpha mAb treatment, resulting in a significant rise in the Th1:Th2 ratio. In addition, an increase in the number of CD4+ T cells expressing the homing receptor CD49d in high density was observed after treatment, which correlated positively with the increase in the Th1:Th2 ratio. Conclusion. We show that the Th1:Th2 ratio in the peripheral blood is raised by anti-TNFalpha mAb treatment.

Quantitation of interferon gamma- and interleukin-4-producing T cells in synovial fluid and peripheral blood of arthritis patients.

OBJECTIVE: The balance between T cells able to produce interferon gamma (IFN-gamma) (type 1) and interleukin-4 (IL-4) (type 2) is considered to be important in the development of autoimmunity. In this study, we quantitated the percentage of both cell types in synovial fluid (SF) and peripheral blood (PB) of rheumatoid arthritis (RA) patients, non-rheumatoid arthritis patients and healthy controls. METHODS: After short-term stimulation of synovial mononuclear cells with phorbol ester and ionomycin, cytokine-producing cells were quantitated using an intracellular staining technique and flow cytometric analysis. RESULTS: Although no significant differences in CD8 + cells were found, significantly higher percentages of IFN-gamma-producing CD4 + (Th 1) and IL-4-producing CD4 + (Th2) cells were found in the peripheral blood of RA patients in comparison with healthy controls. However, the Th1/Th2 ratio was not different between the two groups. Comparative studies between PB and SF showed that in both RA and non-RA patients, percentages of Th1 cells were higher in SF than in PB, while Th2 cells were preferentially found in the PB, resulting in a higher Th1/Th2 ratio in the SF. The Th1/Th2 ratio in the SF correlated with disease activity as estimated by the erythrocyte sedimentation rate. CONCLUSION: These results are in agreement with the hypothesis that Th1 cells preferentially home to inflamed joints in both RA and non-RA patients, but show that this does not result in an altered Th1/Th2 ratio in the PB of RA patients.