Details

Autor(en) / Beteiligte

• Amezcua-Guerra, Luis M
• Espinosa-Bautista, Fernanda
• Hopf-Estandía, Karen
• Valdivieso-Ruiz, Melisa
• Coronel, Dania
• Robledo, Sandra
• Ramos-Rosillo, Varna
• Del Rocío Martínez-Alvarado, María
• Patlán, Mariana
• Páez, Araceli
• Silveira, Luis H
• Tavera-Alonso, Claudia
• Massó, Felipe
• Soto-Fajardo, Carina
• Pineda, Carlos

Titel

Senescent CD4 + CD28 null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study

Ist Teil von

• Clinical rheumatology, 2023-08, Vol.42 (8), p.2181

Ort / Verlag

Germany

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• To characterize CD4 CD28 cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4 CD28 /CD4 cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet cells (98.5% vs. 6.6%; p = 0.001) and few RORγt cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4 cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4 CD28 cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4 CD28 T-bet cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4 CD28 GATA-3 cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4 CD28 RORγt cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4 CD28 cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4 cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.