Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis.

BACKGROUND: Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear. METHODS: In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed. RESULTS: Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression. CONCLUSIONS: Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.

[Adjusting Platelet Counts for Platelet Aggregation Tests].

OBJECTIVE: To explore a better method to adjust platelet counts for light transmission aggregometry (LTA). METHODS: Blood samples from 36 healthy participants aged from 18 to 50 yr. were collected.Platelet-rich plasma (PRP) was diluted using platelet-poor plasma (PPP) and physiological saline (PS),respectively,in a ratio of 1.5,2,2.5 and 3 times. Platelet aggregation was induced by adenosine diphosphate (ADP),arachidonic acid (ARA),collagen (COL), epinephrine (EPI),or ristocetin (RIS). The maximal aggregation rates (MAs) of different approaches were compared. We also compared the MAs induced by RIS between PRP-obtained-PPP and whole blood-obtained-PPP (2 100×g, 5 min). RESULTS: Compared with the original PRP,the MAs induced by ADP,ARA,and EPI decreased in PPP-adjusted PRP (significant at 2-3 times dilution ratio,P<0.05),but not in PS-adjusted PRP (P>0.05). The MA induced by RIS decreased in PS-adjusted PRP (significant at all dilution ratios,P<0.05),but not in PPP-adjusted PRP (P>0.05). No changes in the MA induced by COL were found in PS-adjusted PRP and PPP-adjusted PRP (P>0.05). Whole blood-obtained-PPP (2 100×g, 5 min) had the same MA induced by ristocetin compared with PRP-obtained-PPP (P>0.05). CONCLUSION: PS is recommended for adjusting platelets counts for platelet aggregation induced by ADP,ARA,COL and EPI. Whole blood-obtained-PPP (2 100 ×g, 5 min) is recommended for RIS-induced aggregation as a matter of convenience.

[Clinical Significance of Coagulation Indicators and their Correlation with Inflammatory Factors in Critical Patients with Thromboembolism].

OBJECTIVE: To evaluate the levels of coagulation indicators [thrombomodulin(TM)/ thrombin-antithrombin complexes(TAT)/ α2-plasmin inhibitor-plasmin complexes(PIC)/ tissue plasminogen activator-inhibitor complexes(t-PAIC) /D-Dimer(D-D)/fibrin degradation products(FDP)] in the critical patients with thromboembolism, analyse their correlation with inflammatory factor (procalcitonin/C reactive protein/ interleukin-6), and explore the diagnostic significance of coagulation indicators for these patients. METHODS: The serum levels of the coagulation indicators (TM/TAT/PIC/t-PAIC/D-D /FDP) and inflammatory factors (PCT/IL-6/CRP) were detected in the patient group with critical thromboembolism (n= 38) and critical patient group without thromboembolism as control (n= 81) . The correlation of coagulation indicators with inflammatory factors was analyzed. RESULTS: The values of TM/TAT/PIC/D-D/FDP in thromboembolism group were statistically significantly higher than those in control group (P<0.05). However, the t-PAIC values were not significantly different (P>0.05), and 3 inflammatory factors (PCT/CRP/IL-6) in thromboembolism patients were significantly higher than those in control group (P<0.05). The correlation analysis suggested that the correlation coefficients of TM with PCT, CRP and IL-6 were 0.288, 0.249 and 0.270, respectively (P<0.05). CONCLUSION: The critical patients with thromboembolism show an obviously higher systemic inflammatory response, and accompany with coagulation dysfunction. There is a network relationship between inflammation and coagulation, the interaction of inflammatory factors with coagulation indicators promotes thromboembolism and inflammation.