Three cases of relapsed eosinophilic sinusitis without eosinophilia during mepolizumab maintenance therapy for eosinophilic granulomatosis with polyangiitis.

We present three cases of eosinophilic granulomatosis with polyangiitis (EGPA) where patients experienced relapse of eosinophilic sinusitis without peripheral eosinophilia while on remission maintenance therapy with mepolizumab (MPZ), an anti-interleukin (IL)-5 monoclonal antibody. Despite the initial control of symptoms with high-dose prednisolone (PSL) and MPZ, patients experienced a relapse of nasal obstruction and eosinophilic infiltration in nasal mucosal biopsies. Notably, relapses occurred despite normal peripheral eosinophil counts, indicating the localized nature of eosinophilic inflammation. While IL-5 inhibitors effectively reduce peripheral blood eosinophils, eosinophilic sinusitis may persist due to local factors such as IL-4-mediated inflammation. IL-4 has been implicated in promoting eosinophil migration into nasal tissues, suggesting that IL-5 inhibitors alone may not sufficiently suppress eosinophilic infiltration in such cases. These findings highlight the importance of considering the possibility of eosinophilic sinusitis relapse in EGPA patients treated with IL-5 inhibitors and reduced glucocorticoid doses. Further research is warranted to elucidate the mechanisms underlying local eosinophilic inflammation and optimize treatment strategies for EGPA patients.

Tacrolimus Treatment for TAFRO Syndrome.

TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus.

Subarachnoid Hemorrhaging with Multiple Cerebral Artery Stenoses after Initiating Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: a Case Report.

We encountered a 64-year-old Japanese woman who developed subarachnoid hemorrhaging (SAH) with multiple cerebral artery stenoses during remission induction therapy for eosinophilic granulomatosis and polyangiitis (EGPA). The treatment involved intensified steroid pulse therapy and continued intravenous cyclophosphamide pulse therapy, which led to beneficial effects. Given the rarity of multiple EGPA-associated cerebral artery stenoses and SAH, it is crucial to differentiate them from other diseases. The mortality rate of EGPA complicated by intracranial hemorrhagic lesions, including SAH, is high. When headache is present at the onset of EGPA, the possibility of SAH must be considered.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis.

OBJECTIVES: To examine the effectiveness and drug tolerability of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitor (JAKi) monotherapy in patients with rheumatoid arthritis (RA) in a multicentre cohort study. METHODS: Patients with RA initiated with bDMARD/JAKi monotherapy without conventional synthetic DMARDs were included. Monotherapy regimens were categorised as interleukin-6 receptor inhibitors (IL-6Ri), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKi, or tumour necrosis factor inhibitors (TNFi). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) at 24 weeks, and drug retention was compared among monotherapy using IPW Cox proportional hazards models. RESULTS: A total of 849 treatment courses from 635 patients were included (IL-6Ri, 218; CTLA4Ig, 183; JAKi, 92; TNFi, 356). The difference in change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than TNFi, while that of CTLA4Ig and JAKi was similar with that of TNFi (-0.20 [-0.48 to 0.08], -0.25 [-0.67 to 0.16], respectively). IL-6Ri use was associated with significantly lower overall drug discontinuation than TNFi use (hazard ratio = 0.55 [0.39-0.78], P = 0.001). Similar retention rates were identified among CTLA4Ig and JAKi compared to TNFi. CONCLUSION: In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi, and TNFi monotherapy.

Instability of harmonized thyroid-stimulating hormone immunoassays in clinical practice.

OBJECTIVE: Thyroid-stimulating hormone (TSH) harmonization is effective in minimizing differences between the results of immunoassays in healthy subjects. However, the effectiveness of TSH harmonization in clinical practice has not been investigated. The aim of this study was to evaluate the instability of TSH harmonization in clinical practice. METHODS: We compared the reactivities of four harmonized TSH immunoassays using combined difference plots of 431 patients. We selected patients with statistically significant deviations in TSH levels and analyzed their thyroid hormone levels and clinical characteristics. RESULTS: The combined difference plots showed that one harmonized TSH immunoassay exhibited markedly different reactivity even after TSH harmonization compared with the other three immunoassays. Among 109 patients with mild-to-moderate elevation of TSH levels, we selected 15 patients with statistically significant deviations in TSH levels according to the difference plots of three harmonized TSH immunoassays, excluding one immunoassay that showed different reactivity. The thyroid hormone levels of three patients were misclassified as hypothyroidism or normal due to deviating TSH levels. In terms of clinical characteristics, these patients were in poor nutritional status and general condition, possibly due to their severe illness (e.g., advanced metastatic cancer). CONCLUSION: We have confirmed that TSH harmonization in clinical practice is relatively stable. However, some patients showed deviating TSH levels in the harmonized TSH immunoassays, indicating the need for caution, particularly in poorly nourished patients. This finding suggests the presence of factors that contribute to the instability of TSH harmonization in such cases. Further investigation is warranted to validate these results.

Comparison of the drug retention and reasons for discontinuation of tumor necrosis factor inhibitors and interleukin-6 inhibitors in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

BACKGROUND: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model. RESULTS: Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59-0.86, p < 0.001). The adjusted cumulative incidence of discontinuation due to lack of effectiveness was lower with the IL-6i (HR = 0.46, 95%CI = 0.33-0.63, p < 0.001) while those due to adverse events (HR = 0.82, 95%CI = 0.56-1.18, p = 0.28) or achievement of clinical remission (HR = 1.09, 95%CI = 0.62-1.91, p = 0.76) were similar between the two groups. CONCLUSIONS: In EORA patients initiating a TNFi or IL-6i, significantly higher drug retention was observed with IL-6i. Discontinuation due to lack of effectiveness was significantly less frequent in IL-6i while discontinuations due to adverse event or achievement of clinical remission were similar between the two groups.

Expression of a novel type of KMT2A/EPS15 fusion transcript in FLT3 mutation-positive B-lymphoblastic leukemia with t(1;11)(p32;q23).

The t(1;11)(p32;q23) translocation is a rare but recurrent cytogenetic aberration in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL). This translocation was initially shown to form a fusion gene between KMT2A exon 8 at 11q23 and EPS15 exon 2 at 1p32 in AML. Activating mutations of FLT3 are frequently found in AML but are very rare in ALL. Here, we describe a 75-year-old woman who was diagnosed with B-ALL since her bone marrow was made up of 98.2% lymphoblasts. These blasts were positive for CD19, CD22, CD79a, CD13, and CD33 but negative for CD10 and myeloperoxidase. The karyotype by G-banding and spectral karyotyping was 46,XX,t(1;11)(p32;q23). Expression of KMT2A/EPS15 and reciprocal EPS15/KMT2A fusion transcripts were shown: KMT2A exon 8 was in-frame fused to EPS15 exon 12, indicating that this fusion transcript was a novel type. Considering three reported B-ALL cases, EPS15 breakpoints were markedly different between AML (exon 2) and B-ALL (exons 10-12). Furthermore, an uncommon type of FLT3 mutation in the juxtamembrane domain was detected: in-frame 4-bp deletion and 10-bp insertion. Accordingly, our results indicate that the novel type of KMT2A/EPS15 fusion transcript and FLT3 mutation may cooperate in the pathogenesis of adult B-ALL as class II and class I mutations, respectively.

Neuroendocrine carcinoma and mixed neuroendocrine‒non-neuroendocrine neoplasm of the stomach: a clinicopathological and exome sequencing study.

The gene mutation profiles of gastric neuroendocrine neoplasms are incompletely understood. The purpose of this study was to characterize the molecular pathology of poorly differentiated neuroendocrine carcinoma (NEC) and mixed neuroendocrine‒non-neuroendocrine neoplasm (MiNEN) of the stomach. Surgical cases of gastric NEC (n = 7) and MiNEN (n = 6) were examined by clinical review, immunohistochemistry, microsatellite instability (MSI) analysis and whole-exome sequencing. NEC cases consisted of small- (n = 2) and large-cell types (n = 4). All cases of MiNEN were histologically composed of large-cell type NEC and tubular adenocarcinoma. Whole-exome sequencing analysis detected recurrent mutations in TP53 in 8 cases (62%), and they were more frequently observed in MiNEN than in NEC (100% vs. 29%). Frameshift mutations of APC were observed in two cases of MiNEN. One case of large-cell type NEC had a frameshift mutation with loss of heterozygosity in RB1. The other mutated genes (e.g., ARID1 and KRAS) were detected in a single case each. A high level of MSI was confirmed in one case of MiNEN, which harbored mutations in two well-differentiated neuroendocrine tumor (NET)-related genes (MEN1 and ATRX1). In cases of MiNEN, two histological components shared mutations in TP53, APC and ZNF521, whereas alterations in CTNNB1, KMT2C, PTEN and SPEN were observed in neuroendocrine components only. In conclusion, TP53 is a single, frequently mutated gene in gastric NEC and MiNEN, and alterations in other genes are less common, resembling the mutation profiles of gastric adenocarcinomas. Gene mutations frequently observed in well-differentiated NET were uncommon but not entirely exclusive.

Lymphoplasmacytic lymphoma in a patient with Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disease characterized by benign skin hamartomas, pulmonary cysts leading to spontaneous pneumothorax, and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin (FLCN) gene, a putative tumor suppressor, which result in loss of function of the folliculin protein and may cause cancer predisposition. In a 45-year-old woman with anemia, lymphadenopathy, and a history of recurrent spontaneous pneumothorax, 18F-FDG PET/CT detected diffuse and slight 18F-FDG accumulation in the bone marrow, enlarged spleen, and systemic multiple enlarged lymph nodes. Genetic examination identified a germline nonsense mutation [c.998C > G (p.Ser333*)] on exon 9 of FLCN. Pathological examination of the lymph node revealed a diffuse neoplastic proliferation of plasmacytoid lymphocytes. The neoplastic lymphoid cells were positive for CD20, CD138, and light chain kappa as per immunohistochemistry and mRNA in situ hybridization, and a MYD88 gene mutation [c.755T > C (p.L252P)] was identified. Accordingly, she was diagnosed with lymphoplasmacytic lymphoma concomitant with BHD syndrome. To the best of our knowledge, this is the first report describing the development of hematological malignancy in a patient with BHD syndrome. The FLCN mutation might contribute lymphomagenesis as an additional mutation cooperating with the MYD88 mutation.

Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4.

OBJECTIVES: Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS: The induction of pro-inflammatory cytokines, chemokines, and mediators by sCD14 stimulation of RA-FLS was quantified by real-time PCR and ELISA. Cell proliferation was assessed by the BrdU assay. LPS-RS, a Toll-like receptor 4 (TLR-4) antagonist, was used to block TLR-4 signaling. RESULTS: Soluble CD14 induced the expression of IL-6 mRNA and secretion of the protein. The expression of other pro-inflammatory cytokines and mediators, such as TNF-α, IL-8, intercellular adhesion molecule-1 (ICAM-1), MMP-3, and RANK ligand (RANKL), was also induced by sCD14. In addition, sCD14 stimulation promoted RA-FLS proliferation. LPS-RS abolished IL-6, IL-8, and ICAM-1 mRNA induction by sCD14 in RA-FLS. On the other hand, TNF-α and IL-17A increased TLR-4 expression by RA-FLS and amplified their sCD14-induced IL-6 expression. CONCLUSIONS: Soluble CD14 transmits inflammatory signals to RA-FLS via TLR-4. The effects of sCD14 may be augmented in inflammatory milieu. Our results suggest that sCD14 is involved in the pathogenesis of RA and may be a novel therapeutic target.

Detection of Bacterial Infection Based on Age-Specific Percentile-Based Reference Curve for Serum Procalcitonin Level in Preterm Infants.

BACKGROUND: Considering the physiological changes in serum procalcitonin (PCT) levels in newborns due to age, we recently established an age-specific percentile-based reference curve for serum PCT level. The present study aimed to determine the best cutoff percentile line using this reference curve for the differentiation between infected and colonized preterm infants. METHODS: A total of 52 preterm infants with positive bacterial culture (9 with bacterial infection, 43 with colonization) were enrolled within the study period. The 97.5th, 95.0th, 92.5th, 90.0th, 80.0th, 70.0th, 60.0th, and 50.0th percentile lines were drawn in the reference curve. PCT levels in infected or colonized infants were used, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The best cutoff percentile line was determined in the receiver operating characteristic curve analysis. RESULTS: Of the 52 preterm infants, 9 were infected (5 and 4 infants with an onset of < 7 days and ≥ 7 days after birth, respectively), whereas 43 were colonized (6 and 37 infants with an onset of < 7 days and ≥ 7 days after birth, respectively). The best cutoff percentile lines were the 90.0th percentile (sensitivity, 0.800; specificity, 0.833; PPV, 0.800; NPV, 0.833) and 97.5th percentile (sensitivity, 1.00; specificity, 0.973; PPV, 0.800; NPV, 1.00) in infants with an onset of < 7 days and ≥ 7 days after birth, respectively. CONCLUSIONS: The age-specific percentile-based reference curve for serum PCT level is clinically applicable as a new tool for diagnosing infections in preterm infants with positive culture results, particularly at ≥ 7 days after birth.

Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).

Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nucleotide 3464. To our knowledge, this CBFB-MYH11 fusion transcript has never been reported previously. The clinical characteristics of the present case are in line with previous reports suggesting that rare CBFB-MYH11 fusion transcripts lead to aberrant characteristics such as an atypical cytomorphology and additional cytogenetic abnormalities.

Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients.

OBJECTIVES: Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30-40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). METHODS: We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. RESULTS: Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. CONCLUSION: By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.

Additive effects of inhibiting both mTOR and glutamine metabolism on the arthritis in SKG mice.

Glutamine metabolism and the mechanistic target of rapamycin (mTOR) pathway are activated cooperatively in the differentiation and activation of inflammatory immune cells. But the combined inhibition of both pathways was rarely investigated. This study investigated how inhibiting both glutamine metabolism with 6-diazo-5-oxo-L-norleucine (DON) and mTOR with rapamycin affects immune cells and the arthritis in a mouse model. We revealed that rapamycin and DON additively suppressed CD4+ T cell proliferation, and both of them inhibited Th17 cell differentiation. While DON inhibited the differentiation of dendritic cells and macrophages and facilitated that of Ly6G+ granulocytic (G)-MDSCs more strongly than did rapamycin, G-MDSCs treated with rapamycin but not DON suppressed CD4+ T cell proliferation in vitro. The combination of rapamycin and DON significantly suppressed the arthritis in SKG mice more strongly than did each monotherapy in vivo. The numbers of CD4+ T and Th17 cells in the spleen were lowest in mice treated with the combination therapy. Thus, combined treatment with rapamycin and DON additively ameliorated the arthritis in SKG mice, possibly by suppressing CD4+ T cell proliferation and Th17 differentiation. These results suggest the combination of rapamycin and DON may be a potential novel therapy for arthritis.

MicroRNA-124 inhibits TNF-α- and IL-6-induced osteoclastogenesis.

Receptor activator for nuclear factor κB ligand (RANKL)-independent osteoclastogenic pathway was reported recently. MicroRNA (miR)-124 has been known to suppress RANKL-dependent osteoclastogenesis by inhibiting NFATc1 expression. However, whether miR-124 regulates a RANKL-independent pathway has not been elucidated. In this study, we examined whether a RANKL-independent pathway is regulated by miR-124 in addition to the RANKL-dependent one. Using osteoclastogenic culture and pit-formation assay, we found that a miR-124 mimic inhibited osteoclastogenesis in mouse bone marrow-derived macrophages stimulated by TNF-α, IL-6, and M-CSF in the presence of osteoprotegerin. We also showed that the expression levels of osteoclast-specific genes and NFATc1 protein were suppressed in the miR-124 mimic-transfected cells by performing quantitative-polymerase chain reaction and western blotting. Our results indicate that miR-124 is important in inhibiting both RANKL-dependent and -independent osteoclast differentiation by suppressing NFATc1-mediated pathway.

Progression of immunoglobulin G4-related disease to systematic lupus erythematosus after gastric cancer surgery: A case report.

RATIONALE: Immunoglobulin G4 related disease (IgG4-RD) rarely coexists with other autoimmune diseases, though we had a patient whose primary clinical problem was shifted from IgG4-RD to systemic lupus erythematosus (SLE) after gastrectomy. The present paper aimed to report pathological findings and clinical course of the patient. PATIENT CONCERNS: The patient was a male aged 74 years old with gastric cancer characterized by the following symptoms: Raynaud phenomenon, polyarthralgia, and swollen parotid glands on both sides. Before gastrectomy, laboratory examination results showed renal dysfunction, hypocomplementemia, antinuclear antibodies (ANAs) positivity, and elevated serum IgG and IgG4 levels. DIAGNOSIS: Based on postoperative renal biopsy showing severe plasma cell infiltration with tubulointerstitial fibrosclerosis, the patient was diagnosed with IgG4-RD. Despite significant improvement in renal function and reduction in parotid gland swelling during the postoperative follow-up period, after 7 months of the gastrectomy, anti-DNA antibody levels were increased and serositis was detected, which indicated the onset of SLE. IgG4-type ANA were also detected in the sera of the patient. INTERVENTIONS: Treatment by oral prednisolone at 30 mg/day was initiated. OUTCOMES: Pericardial fluid, pleural effusions, and thickening of the gallbladder wall improved after 3 months of treatment according to computed tomography. LESSONS: This study presented a rare case of comorbidity, wherein the patient's primary problem progressed from IgG4-type ANA-positive IgG4-RD to SLE after excision of gastric cancer.

Myeloid-derived suppressor cells in non-neoplastic inflamed organs.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a highly heterogeneous population of immature myeloid cells with immunosuppressive function. Although their function in tumor-bearing conditions is well studied, less is known about the role of MDSCs in various organs under non-neoplastic inflammatory conditions. MAIN BODY: MDSCs are divided into two subpopulations, G-MDSCs and M-MDSCs, and their distribution varies between organs. MDSCs negatively control inflammation in inflamed organs such as the lungs, joints, liver, kidneys, intestines, central nervous system (CNS), and eyes by suppressing T cells and myeloid cells. MDSCs also regulate fibrosis in the lungs, liver, and kidneys and help repair CNS injuries. MDSCs in organs are plastic and can differentiate into osteoclasts and tolerogenic dendritic cells according to the microenvironment under non-neoplastic inflammatory conditions. CONCLUSION: This article summarizes recent findings about MDSCs under inflammatory conditions, especially with respect to their function and differentiation in specific organs.