Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

New-onset Polymyalgia Rheumatica Following the Administration of the Pfizer-BioNTech COVID-19 Vaccine.

We herein report the case of an 80-year-old Japanese woman who presented to our hospital with bilateral pain in the shoulders and hips lasting for a month since 2 days after the second dose of the BNT162b2 COVID-19 vaccine. Her physical findings, laboratory data, and ultrasonographic findings of bilateral biceps tenosynovitis and lateral subacromial bursitis were consistent with a diagnosis of polymyalgia rheumatica (PMR). She was successfully treated with oral prednisolone 15 mg/day. Although a causal relationship could not be definitively confirmed, PMR should be considered as a differential diagnosis in cases of persistent myalgia after administration of the BNT162b2 vaccine.

Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study.

Psychiatric manifestations are relatively common in systemic lupus erythematosus (SLE) patients. Since there are factors causing psychiatric manifestations other than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE patients with neuropsychiatric manifestation. The current studies were therefore designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter retrospective study was performed with 45 SLE patients who showed psychiatric manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to causes other than SLE (non-LP) was confirmed by retrospective review of the clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the retrospective study. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5% and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results indicate that CSF IL-6 might be an effective measure in diagnosing LP, although exclusion of infectious meningoencephalitis and cerebrovascular accident is necessary.

Chemoattractant mechanism of Th1 cells in class III and IV lupus nephritis.

Proliferative lupus nephritis (PLN) is the common, severe, and important form of lupus nephritis. Recent report showed that T cells producing Interferon (IFN)gamma (Th1 cells) increased in patients with World Health Organization class IV. However, the relation between the increase of Th1 cells and the pathogenesis has been made unclear. The aim of this study was to examine the chemoattractant mechanism of Th1-producing cells and whether in vitro IFNgamma secretion from Th1-producing cells in PLN. The Th1:Th2 ratio in peripheral blood was measured by flow cytometry. The serum levels of IL-2, IFNgamma, IL-13, monocyte chemoattractant protein-1 (MCP-1) and IP-10 were determined by using enzyme-linked immunosorbent assay. In in vitro IFNgamma production assay, CD4(+)T cells co-cultured with IL-12 and/or IL-18. Th1:Th2 ratio in PLN was high and not correlated with the serum Th1 cytokine level. This Th1-producing cell tended to go toward the inflammatory lesion by low CD62L expression and chemokines. The level of MCP-1 and IP-10 in patients with PLN significantly increased. Lastly, in vitro IFNgamma production assay, patients with PLN CD4(+)T cells produced IFNgamma by the addition of IL-12 and IL-18, while CD4(+)T cells in normal controls did not produce. These findings suggest that combination of Th1 inducers and chemokine inhibition might be powerful threrapeutic approach in PLN.

Decrease in CD4+CD25+ and CD8+CD28+ T cells in interstitial pneumonitis associated with rheumatic disease.

The expression of CD25 or CD28 on T cells was examined in patients with rheumatic diseases associated with interstitial pneumonitis (IP), in order to investigate the conditions of CD4+CD25+ regulatory T cells and CD8+CD28- suppressor T cells. Fifty-five patients with various rheumatic diseases and 23 normal controls were enrolled. CD4+CD25+ T cells of patients with IP were significantly decreased in comparison with non-IP patients, and the ratio of CD8+CD28- T cells in patients with IP was significantly higher than that in non-IP patients or normal controls. These results for CD8+CD28- T cells were in accord with the decrease in CD8+CD28+ T cells, and may be related to activation-induced CD8+CD28+ T-cell death. Thus, the abnormality of CD4+CD25+ regulatory T cells may be related to the pathogenesis of IP, and the survival and activation of CD8+ T cells.

Expression of CD22 on peripheral B cells in patients with rheumatoid arthritis: relation to CD5-positive B cells.

B cells in patients with rheumatoid arthritis (RA) are hyperactivated. Although B cell receptor signal transduction may be affected by various response regulators, CD22 plays an important role as a response regulator of B cells. Therefore, we investigated and examined CD22 expression on peripheral blood B cells of patients with RA. Thirty-two RA patients and 16 controls were enrolled in this study, and CD22 expressions on B cells were analyzed by flow cytometry. In patients with RA, CD22(+) B cells significantly decreased in comparison to the controls (ratio: P < 0.05). However, there was no correlation between this decrease and the clinical data. Interestingly, CD5(+) CD22(-) B cells significantly increased in RA patients. The decrease in CD22(+) B cells and increased in CD5(+)CD22(-) B cells play critical roles in the pathogenesis of RA mediated by the activation of B cells.

Down-regulation of CD72 and increased surface IgG on B cells in patients with lupus nephritis.

The significance of both the acceleratory and inhibitory functions of the CD72 molecule was investigated among patients with systemic lupus erythematosus (SLE) during modification of B cell differentiation. Expression of the CD72 molecule and mRNA on B cells was decreased in SLE with lupus nephritis, while CD100 expression on both CD4+ T cells and CD8+ T cells was not significant in comparison with the controls. When the relationship between CD72 expression and other B cell markers was examined, decreased expression of CD72 was associated with differences in the stage of differentiation. In patients with decreased expression of CD72, switching to IgG was evident, and the disease stage was started to severe. In patients with lupus nephritis, the decreased expression of CD72 was related to class switching on B cells, suggesting that CD72 is a useful marker for determining class switching of B cells in lupus nephritis.

CD19/22 balance relates to improvement of disease activity in systemic lupus erythematosus.

B cells in patients with systemic lupus erythematosus (SLE) are hyperactivated and B-cell receptor signal transduction may be affected by various response regulators. CD19 and CD22 play a major role as regulators of B-cell response. Therefore, we examined CD19 and CD22 expressions on B cells of patients with SLE, and how they were related to disease activity. Thirty-one patients with active SLE were selected and enrolled in this study. Evaluation of CD19 and CD22 expressions on B cells was performed prior to and after treatments with flow cytometry analysis. Disease activity was determined according to the SLE disease activity index score. CD19 and CD22 expressions on B cells in SLE patients revealed no significant differences when compared with the controls. However, improvement of SLE was recognized among patients with an increased ratio of CD22-positive cells. Our results suggest that this balance is a useful marker for determining improvement of SLE disease activity, although the CD19/22 balance does not contribute to the pathogenesis of SLE.