IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells. We also found that the percentage of programmed death 1 circulating Tfh cells in IgG4-DS patients was higher than that in healthy volunteers and was well correlated with clinical parameters. Our findings indicate that anomalous Tfh cells in tissue lesions of IgG4-RD have features distinct from those in lymphoid counterparts or blood and potentially regulate local IgG4 production in IgG4-RD.
Objective
The aim was to study the pathological role of lymphocytes with a peripheral T helper-cell-like phenotype (PD-1
+
CXCR5
−
CD4
+
) in IgG4-related disease (IgG4-RD).
Methods
PD-1
+
CXCR5
−
CD4
+
T cells in the blood of patients with IgG4-RD (
n
= 53), patients with SS (
n
= 16) and healthy volunteers (
n
= 34) as controls were analysed by flow cytometry. Correlations between results obtained by flow cytometry and clinical parameters relevant to IgG4-RD were also analysed.
Results
The percentage and absolute number of PD-1
+
CXCR5
−
cells within total CD4
+
T cells in IgG4-RD patients were significantly increased compared with those in healthy volunteers. Further analysis showed that there were marked positive correlations of the percentage of PD-1
+
CXCR5
−
CD4
+
T cells with the serum level of IgG4 and the number of organs involved. Interestingly, granzyme A (GZMA)
+
cells were enriched in PD-1
+
CXCR5
−
CD4
+
T cells, and the percentage and absolute number of GZMA
+
PD-1
+
CXCR5
−
CD4
+
T cells were significantly elevated in IgG4-RD patients. Although no obvious change was observed in the percentage of total CD4
+
T cells, the percentage and absolute number of PD-1
+
CXCR5
−
CD4
+
T cells decreased in accordance with a reduction of serum IgG4 level after treatment with glucocorticoids.
Conclusion
In IgG4-RD, circulating CD4
+
T-cell populations were composed of PD-1
+
CXCR5
−
cells, and the ratios of these cells were correlated with clinical manifestations of IgG4-RD. Further analysis of GZMA
+
PD-1
+
CXCR5
−
CD4
+
T cells might lead to a deeper understanding of the pathogenesis of ectopic lymphoid follicles and the persistent inflammation in IgG4-RD.
The present research showed that significant adverse effects on mental health were observed among women who experienced IPV with sexual violence compared with the ones without. These findings provide important implications for considering the specific approaches to meet the needs of those women experiencing sexual IPV and the need for timely and effective interventions, including healthcare, social services, and primary prevention.
This study assessed the psychometric properties of the Japanese version of the Eyberg Child Behavior Inventory (ECBI) in children in clinical and non‐clinical settings in Japan. Validation of the ECBI for clinical and non‐clinical participants (N = 128, 2–7 years of age) was evaluated. First, we evaluated the internal consistency reliability of the ECBI Problem and Intensity scales. We evaluated the construct and criterion‐referenced validity by comparing scores among the subscales of the ECBI, Child Behavior Checklist (CBCL), and Japanese versions of the Parenting Stress Index‐Short Form (PSI‐SF) and the Beck Depression Inventory‐II (BDI‐II). Results showed that Cronbach's alphas for both the Intensity and Problem scores were .91 and .92, respectively, which reflects high internal consistency. Results also showed that both the ECBI Intensity and Problem scores were significantly correlated with all subscales of the CBCL, PSI‐SF, and BDI‐II. These data suggest that the Japanese version of the ECBI is a psychometrically sound measure for assessing behavior problems in Japanese children.
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