In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8⁺CD39⁻CD73⁺ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39⁺CD73⁺ and CD39⁻CD73⁻ cells. Good responders tended to have lower B CD39⁺CD73⁺ cell percentages at baseline and 3 months. Additionally, Treg, CD8⁺ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4⁺ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4⁺ and CD8⁺ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.

Background: Giant cell arteritis (GCA) is a heterogeneous disease with diverse clinical presentations and varying degrees of severity. This study aimed to assess the incidence of 3 clinical subsets in GCA and analyze associated severe complications and survival rates. By identifying distinct clinical patterns, the goal is to customize treatment approaches and minimize severe complications during follow-up. Methods: This retrospective study classified clinical manifestations of GCA into 3 major phenotypes based on the reason for consultation: i) cranial, ii) extracranial, and iii) occult GCA. These groups were analyzed and compared for acute complications, including severe ischemic complications, “true” occlusive disease, and late complications such as aortic aneurysm. Survival data were also collected during follow-up. Results: Visual disturbances were more common in the cranial GCA group compared to other subsets (P < .001). Blindness and stroke showed a clinically relevant trend, although statistical differences were not significant between the cranial GCA groups. Limb claudication was significantly more prevalent in the extracranial subset compared to the cranial or occult GCA subsets (12% vs. 2.6% vs. 0% respectively). Severe ischemic complications and true occlusive disease were more frequent in the cranial GCA groups (60%, P=.005 and 40%, P=1.64 respectively). Regarding mortality, there were no statistically significant differences in survival among the different clinical subsets. However, the occult GCA subset showed a trend towards a higher prevalence of deaths, both overall and specifically due to GCA. Conclusion: Clinical subsets in GCA present distinct complications and survival outcomes, with the cranial subset showing a higher incidence of severe ischemic events and the occult subset associated with delayed diagnosis and increased mortality. Recognizing these subsets is crucial for tailored treatment approaches and improving patient prognosis. Further prospective studies are needed to refine diagnostic and therapeutic strategies. Cite this article as: Estrada P, Narváez J, Moya P, et al. Clinical phenotypes of giant cell arteritis: insights into complications and survival outcomes. Eur J Rheumatol. 2024;11(2):33-38.

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.

Objective: We aimed to quantify the mortality risk in a large, well-characterized cohort of patients with Sjögren disease (SjD) and to identify independent predictors of mortality in this population.Methods: We included 314 patients diagnosed with SjD according to the 2002 American-European Consensus Group criteria from a prospective, multicenter SjögrenSER Prospective cohort. Detailed data on systemic manifestations, serological markers, disease activity, and mortality were collected after a median of 9.5 (IQR 9.2-9.9) years of follow-up. The primary outcome was overall mortality, and secondary analyses aimed to identify independent predictors of mortality using Cox proportional hazards models. Standardized mortality ratios were calculated by comparing the observed deaths in the SjD cohort to the expected deaths in an age- and sex-matched general population.Results: The study identified a 70% increased mortality risk in the SjD cohort compared to the general population, with a standard mortality ratio of 1.7. Infections (35.7%), malignancies (23.8%), and cardiovascular disease (CVD; 7.1%) were the most common causes of death. Multivariate analysis revealed that older age (HR 1.11/year, 95% CI 1.07-1.15), C4 hypocomplementemia (HR 3.75, 95% CI 1.55-9.06), elevated erythrocyte sedimentation rate (ESR; HR 1.01, 95% CI 1.00-1.03), history of heart failure (HR 4.24, 95% CI 1.02-17.58), and pulmonary involvement (HR 3.31, 95% CI 1.39-7.88) were independent predictors of mortality.Conclusion: This study found a significantly increased mortality risk in SjD, with infections, malignancies, and CVD as leading causes of death. Independent predictors of mortality include advanced age, C4 hypocomplementemia, elevated ESR, heart failure, and pulmonary involvement, underscoring the need for proactive, individualized management.