Plasma Cell Infiltration Research Articles

A Review on The Role of Environmental Exposures in IgG4-Related Diseases.

Immunoglobulin G4-related diseases (IgG4-RDs) are immune-mediated fibroinflammatory multisystemic conditions identified by the presence of tumefactive lesions with a rich infiltrate of IgG4-positive plasma cells, and often by a high IgG4 serum concentration. IgG-RDs have a prevalence of at least 1 case every 100,000 persons, and they are mostly diagnosed after age 50, with a male to female ratio of about 3:1. IgG4-RD pathophysiology is still uncertain: it has been proposed that both genetic predisposition and chronic environmental exposures may play a role by triggering abnormal immune activation that perpetuates the disease. The purpose of this review is to summarize the evidences supporting the hypothesis that certain environmental/occupational exposures can trigger IgG4-RDs, focusing on the possible role of asbestos in an emerging IgG4-RD called idiopathic retroperitoneal fibrosis (IRF). Although some studies suggested a relationship between tobacco smoking and IgG4-RD risk, occupational exposures seem to have the most interesting effects. Positive history of blue-collar work increases the risk of developing an IgG4-RD, and mineral dusts and asbestos were the most strongly associated industrial compounds. Asbestos has been found to be a risk factor for IRF years before its classification as IgG4-RD, and later in two large case-control studies. In the most recent one, conducted on 90 patients and 270 controls, asbestos exposure conferred an increased IRF risk, quantified by odds ratios from 2.46 to 7.07. Further structured studies including serum IgG4 evaluation should be conducted to clarify the effect of asbestos on patients with confirmed diagnosis of IgG4-related IRF. Environmental exposures, especially of occupational origin, appear to play a role in the development of different types of IgG-RDs. In particular, although first suggested very recently, the relationship between asbestos and IRF deserves to be explored in more structured studies, especially because of the biological plausibility of the role of asbestos in IRF pathogenesis.

PLASMA CELL GINGIVITIS TRIGGERED BY TOOTHPASTE

Plasma cell gingivitis is a rare benign condition characterized by the inflammatory infiltration of plasma cells, secondary to a hypersensitivity reaction to allergens found in oral hygiene products. This study aimed to present the case of a 48-year-old female, who was admitted to our clinic complaining of an intense gingival discomfort for the past six months, with the onset of symptoms occurring after using a new toothpaste. Clinical examination revealed generalized gingival erythema and edema. An incisional biopsy was performed, which, through direct immunofluorescence, revealed connective tissue densely permeated by interstitial lymphoplasmohistiocytic inflammatory cells, a condition that must be distinguished from other autoimmune diseases. The diagnosis of plasma cell gingivitis was concluded with a detailed history, differential diagnoses, and histopathology. The elimination of the etiologic factor, namely the toothpaste, and the use of topical corticosteroids improved both the lesions and the symptoms. Plasma cell gingivitis is a rare benign condition characterized by the inflammatory infiltration of plasma cells, secondary to a hypersensitivity reaction to allergens found in oral hygiene products. This study aimed to present the case of a 48-year-old female, who was admitted to our clinic complaining of an intense gingival discomfort for the past six months, with the onset of symptoms occurring after using a new toothpaste. Clinical examination revealed generalized gingival erythema and edema. An incisional biopsy was performed, which, through direct immunofluorescence, revealed connective tissue densely permeated by interstitial lymphoplasmohistiocytic inflammatory cells, a condition that must be distinguished from other autoimmune diseases. The diagnosis of plasma cell gingivitis was concluded with a detailed history, differential diagnoses, and histopathology. The elimination of the etiologic factor, namely the toothpaste, and the use of topical corticosteroids improved both the lesions and the symptoms.

#4041 THE INTERSTITIAL TUBULAR INJURY IN THE COURSE OF LUPUS NEPHRITIS

Abstract Background and Aims Tubulo-interstitial involvement in lupus nephritis (LN) refers to the presence of interstitial fibrosis and tubular atrophy (IFTA) in the renal biopsies of patients with lupus. The impact of these features on patient outcomes has not been fully established. The aim of this study was to determine the correlation between IFTA and patient outcomes in LN. Method A retrospective descriptive study was conducted on 160 patients with systemic lupus erythematosus who underwent renal biopsy between 2020 and 2022. Clinical and biological data, as well as histologic findings, were analyzed to determine the outcomes associated with IFTA in LN. Other causes of tubulointerstitial nephritis like drugs and toxins were excluded. Results The study population consisted of 148 females and 12 males, with a mean age of 37.2 years (ranging from 18 to 62 years) at the time of renal biopsy. Hematuria was observed in 62.5% of patients, nephrotic syndrome in 28.1%, hypertension in 24.3%, and renal failure in 17.5% with a mean proteinuria of 2.4±0.6 g/24 h. ANA was positive in a diffuse pattern in all cases, positive anti-ds-DNA,mean C3 was 29 (84-122 mg/dL), and mean C4 was 16.2 (20-40 mg/dl). Other serology C-ANCA and P-ANCA were all negative as well as negative HBV and HCV serology. However serology for Sjogren's syndrome was positive in 61 cases (41%). The histopathological study showed mild mononuclear and plasma cell infiltration of the interstitium, and tubular hyaline casts in 87% of cases. Examination of renal vessels was unremarkable in 94.5% of cases. IFTA was present in 72 patients (45%), with the most frequent glomerular involvement being LN class IV (55.5%) followed by LN class III (32.4%) with respectively (P = .09, P = .2)and was associated significantly with the anti-DNA antibody titer (P = .003). The severity of these lesions was found to be independently correlated with worsening of renal failure at 6 months follow-up (P = .02). Conclusion The findings of this study suggest that IFTA is a significant prognostic factor for the progression of renal failure in lupus nephritis, regardless of the class of the disease. The pathogenesis of tubulointerstitial lesions seems to be the result of circulating immune complexes specifically interacting with tubulointerstitial autoantigens.

(Smoldering) multiple myeloma: mismatch between tumor load estimated from bone marrow biopsy at iliac crest and tumor load shown by MRI.

In multiple myeloma and its precursor stages, precise quantification of tumor load is of high importance for diagnosis, risk assessment, and therapy response evaluation. Both whole-body MRI, which allows to investigate the complete bone marrow of a patient, and bone marrow biopsy, which is commonly used to assess the histologic and genetic status, are relevant methods for tumor load assessment in multiple myeloma. We report on a series of striking mismatches between the plasma cell infiltration estimating the tumor load from unguided biopsies of the bone marrow at the posterior iliac crest and the tumor load assessment from whole-body MRI.

A Case of Multiple Myeloma with Extremely Rare Manifestation

Introduction: Multiple myeloma (MM) is a neoplastic proliferation of immunoglobulin-producing plasma cells that have multiple presentations due to the infiltration of plasma cells in the bone marrow and other organs. Common manifestations include anemia, bone pain, fatigue, and hypercalcemia. MM presented with rectorrhagia is very rare. Case Presentation: A 74-year-old woman with a history of rectorrhagia episodes from about nine months ago presented with severe anemia, weakness, and lethargy. The findings of endoscopy and colonoscopy did not justify the patient's manifestation, and finally, due to thrombocytopenia and anemia, a bone marrow biopsy was performed, and multiple myeloma was diagnosed. Conclusions: Although GI bleeding in Multiple myeloma is a very rare manifestation, this diagnosis must be considered in the differential diagnosis of patients with unexplained and refractory GI bleeding.

IgG4-related Inflammatory Pseudotumor with Imaging Findings Similar to Meningioma.

IgG4-related inflammatory pseudotumor is a feature of IgG4-related disease and develops in various organs. Intracranial IgG4-related inflammatory pseudotumor is rare, and data on the clinical course and response to treatment are insufficient in the literature. We herein report a patient with IgG4-related inflammatory pseudotumor who had magnetic resonance imaging findings similar to meningioma. Tumorectomy was discontinued because of the intraoperative rapid diagnosis, which revealed the infiltration of lymphocytes and plasma cells. She received oral prednisolone therapy for IgG4-related inflammatory pseudotumor, and the tumor size had significantly decreased after six months of treatment.

Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia

To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

RWD156 The Impact of the Sars-Cov-2 Pandemic (COVID-19) on the Incidence of Newly Diagnosed Multiple Myeloma Patients Using a Federated Network of Real-World Evidence in US and Germany

COVID-19 had an impact on health care, including diagnostics. Early diagnosis of MM is a critical factor for prognosis. We examined the impact of COVID-19 on incidence of NDMM patients and on characteristics in NDMM patients in US and in Germany. 44,164 NDMM patients were identified in TriNetX federated network across 55 healthcare organizations in US between January 2018 and December 2021. A bivariate analysis examined changes in patient characteristics in two cohorts before (Cohort 1; n=25513) and after (Cohort 2; n=18.651) the start of the COVID-19 pandemic in March 2020. 4172 NDMM patients were identified in the German database in a sample of across >100 healthcare organizations in the same time period. Similarly, bivariate analysis examined changes in patient characteristics before (Cohort 1; n=2252) and after (Cohort 2; n=1920) the start of pandemic. Analysis of US data showed a significant decrease in incidence of NDMM. Bivariate analysis revealed that NDMM patients in Cohort 2 have a significantly higher risk profile compared with patients in Cohort 1, higher incidence of renal failure (13.5% v. 15.43%), heart failure (10.3% v 11.26%), bone lesions (12.6% v. 13.05%) and anemia (26.8% v. 29.75%). The German data indicated an increased risk profile in Cohort 2, with higher reporting of renal impairment (12.3% v. 15.5%) and cardiac impairment (8.3% v. 10.9%). The higher risk profile was reflected in a significant increase of all SLiM-CRAB criteria, notably hypercalcemia (24.1 % v. 36.9%), bone marrow plasma cell infiltration (28.1% v. 36.8%) and free light chain involvement (27.3% v. 41.3%). The results provide real-world evidence of a change in risk profile for patients with NDMM during COVID-19. This higher risk profile is observed in both the US and Germany, and may negatively impact outcomes such as progression-free and five-year overall survival.

Endoscopic features of lymphoid follicles in the colonic mucosa using the image enhanced endoscopy and its association with colorectal adenoma.

Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.

Autoantigen-selected B cells are bystanders in spontaneous T cell-driven experimental autoimmune hepatitis.

Autoreactive B cells are considered pathogenic drivers in many autoimmune diseases; however, it is not clear whether autoimmune B cells are invariably pathogenic or whether they can also arise as bystanders of T cell-driven autoimmune pathology. Here, we studied the B cell response in an autoantigen- and CD4+ T cell-driven model of autoimmune hepatitis (AIH), the Alb-iGP_Smarta mouse in which expression of a viral model antigen (GP) in hepatocytes and its recognition by GP-specific CD4+ T cells causes spontaneous AIH-like disease. T cell-driven AIH in Alb-iGP_Smarta mice was marked by autoantibodies and hepatic infiltration of plasma cells and B cells, particularly of isotype-switched memory B cells, indicating antigen-driven selection and activation. Immunosequencing of B cell receptor repertoires confirmed B cell expansion selectively in the liver, which was most likely driven by the hepatic GP model antigen, as indicated by branched networks of connected sequences and elevated levels of IgG antibodies to GP. However, intrahepatic B cells did not produce increased levels of cytokines and their depletion with anti-CD20 antibody did not alter the CD4+ T cell response in Alb-iGP_Smarta mice. Moreover, B cell depletion did not prevent spontaneous liver inflammation and AIH-like disease in Alb-iGP_Smarta mice. In conclusion, selection and isotype-switch of liver-infiltrating B cells was dependent on the presence of CD4+ T cells recognizing liver antigen. However, recognition of hepatic antigen by CD4+ T cells and CD4+ T cell-mediated hepatitis was not dependent on B cells. Thus, autoreactive B cells can be bystanders and need not be drivers of liver inflammation in AIH.

Prediction of Bone Marrow Biopsy Results From MRI in Multiple Myeloma Patients Using Deep Learning and Radiomics.

In multiple myeloma and its precursor stages, plasma cell infiltration (PCI) and cytogenetic aberrations are important for staging, risk stratification, and response assessment. However, invasive bone marrow (BM) biopsies cannot be performed frequently and multifocally to assess the spatially heterogenous tumor tissue. Therefore, the goal of this study was to establish an automated framework to predict local BM biopsy results from magnetic resonance imaging (MRI). This retrospective multicentric study used data from center 1 for algorithm training and internal testing, and data from center 2 to 8 for external testing. An nnU-Net was trained for automated segmentation of pelvic BM from T1-weighted whole-body MRI. Radiomics features were extracted from these segmentations, and random forest models were trained to predict PCI and the presence or absence of cytogenetic aberrations. Pearson correlation coefficient and the area under the receiver operating characteristic were used to evaluate the prediction performance for PCI and cytogenetic aberrations, respectively. A total of 672 MRIs from 512 patients (median age, 61 years; interquartile range, 53-67 years; 307 men) from 8 centers and 370 corresponding BM biopsies were included. The predicted PCI from the best model was significantly correlated (P ≤ 0.01) to the actual PCI from biopsy in all internal and external test sets (internal test set: r = 0.71 [0.51, 0.83]; center 2, high-quality test set: r = 0.45 [0.12, 0.69]; center 2, other test set: r = 0.30 [0.07, 0.49]; multicenter test set: r = 0.57 [0.30, 0.76]). The areas under the receiver operating characteristic of the prediction models for the different cytogenetic aberrations ranged from 0.57 to 0.76 for the internal test set, but no model generalized well to all 3 external test sets. The automated image analysis framework established in this study allows for noninvasive prediction of a surrogate parameter for PCI, which is significantly correlated to the actual PCI from BM biopsy.

Clinical and Histopathological Features of an Italian Monocentric Series of Primary Small Bowel T-Cell Lymphomas.

The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical-pathological profile of a series of patients affected by intestinal T-cell lymphomas (ITCL) and possibly define hallmarks of these neoplasms. A total of 28 patients were included: 17 enteropathy-associated T-cell lymphomas (EATL), 5 monomorphic epitheliotropic T-cell lymphomas (MEITL), 3 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (ITCLDGT), and 3 intestinal T-cell lymphomas not otherwise specified (ITCL-NOS). Celiac disease (CD) was diagnosed in around 70% of cases. Diagnosis of EATL showed a significant correlation with CD30 expression, whereas MEITL with angiotropism and CD56 positivity. ITCLDGT cases showed plasma cells infiltration. Peripheral lymphocytosis, the absence of a previous diagnosis of CD, an advanced Lugano clinical stage, and the histological subtype ITCL-NOS were significantly associated with worse survival at multivariate analysis. Our findings about the epidemiological, clinical, and histopathological features of ITCL were in line with the current knowledge. Reliable prognostic tools for these neoplasms are still lacking but according to our results lymphocytosis, diagnosis of CD, Lugano clinical stage, and histological subtype should be considered for patient stratification.

Gynecopathology in the Diagnosis and Assessment of Chronic Endometritis

Objectives: To summarize the gynecopathology findings in the diagnosis and assessment of chronic endometritis (CE) and provide insights into the therapeutics of CE. Mechanism: Chronic endometritis (CE) refers to the inflammatory state of the endometrium, which might alter endometrial receptivity and impact embryo implantation. As a relatively asymptomatic disease, the diagnosis and assessment of CE mainly lies in endometrial biopsy and further morphological and functional examinations. The authors searched the electronic database with a combination of key terms including chronic endometritis, histopathology, hysteroscopy, microbiota, inflammation, vascularization, decidualization as well as autophagy and summarized the current findings.in the diagnosis and assessment of CE. Findings in Brief: Plasma cell infiltration with immune staining, hysteroscopic manifestations including swelling, hyperemia and micropolyps, and pathogenic diagnosis were the main criteria for diagnosing CE. Further assessment of CE revealed the release of proinflammatory cytokines, leukocyte infiltration, enhanced vascularization and autophagy. These factors all contribute to an inflammatory state of the endometrium and decreased flow reserve supplying the embryo, which lead to the pathway explaining implantation failure in CE patients. Conclusions: Gynecopathology plays an essential role in the diagnosis and assessment of CE. Understanding such methods can help to screen out asymptomatic patients and initiate proper treatment, which eventually promotes better knowledge of the relationship between CE and embryo implantation and a higher successful implantation rate.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor

BackgroundSome patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET.Case presentationA 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels.Discussion and ConclusionsThis is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer

BackgroundAlthough immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells.MethodsCrosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis.ResultsBased on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response.ConclusionsPCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients.Graphical

Plasma Cell Gingivitis and Its Mimics.

Plasma cell gingivitis (PCG) is an inflammatory condition that affects the gingival mucosa of the oral cavity. It is characterized by polyclonal dense plasma cell infiltrate in the connective tissue. Lesions do not respond to prophylactic treatment. Etiology is most likely hypersensitivity to certain antigens (eg, toothpastes, oral rinses, chewing gums, spices). Differential diagnosis of PCG includes reactive, granulomatous, and neoplastic lesions. The diagnostic workup is based on patient's history and the clinicopathologic correlation to rule out mimics of PCG. Dermatologic patch test may be indicated in chronic conditions to identify the allergen.

Loss of microRNA-29 in B cells leads to atopic skin phenotype in mice

Abstract Developing B cells are highly dependent on microRNA (miRNA) regulation. We have previously demonstrated the miR-29 family of miRNAs contributes to the regulation of B cell survival through fine-tuning of PTEN expression, a negative regulator of B cell receptor (BCR) signaling. When the miR-29 alleles are selectively deleted in B cells, this leads to reduced survival which can be rescued by ablating one copy of Ptento restore normal BCR signaling. We observed that mice with B cells lacking miR-29 also develop an inflammatory skin phenotype associated with lesions, leukocyte infiltration into the skin, and persistent pruritis. Nearly 50% of miR-29-deficient animals die within 6 months of birth, and ablation of Ptento restore BCR signaling did not improve the survival rate. This suggests that additional targets of miR-29 in B lymphocytes are involved in promoting this inflammatory skin condition. Epidermal thickening, granulocyte plasma cell infiltration in the skin, and high serum IgE titers suggest that miR-29 may contribute to the regulation of IgE-driven immune responses and that in the absence of this miRNA family, animals develop atopic dermatitis. Our bioinformatic analysis revealed that miR29 is predicted to regulate the expression of the Il4Ratranscript, and in vitrodifferentiation assays revealed that miR-29-deficient B cells have a higher propensity for IgE class switch recombination in response to IL-4 and/or IL-13 stimulation compared to wild-type control B cells. We conclude that miR-29 is critical in the regulation of both Ptenand Il4raexpression in mature B cells thereby influencing the survival and function of peripheral B lymphocytes, which can have profound repercussions for the development of autoimmune disease. The Bernard Levine Fellowship

A Case of Demyelinating Neuropathy with Markedly Elevated Serum IgG4 Levels and Anti-Contactin 1 IgG4 Antibody.

We herein report a 77-year-old man with a 4-month history of progressive gait and sensory disturbances of the extremities. A nerve conduction study indicated demyelinating polyneuropathy. Serum IgG4 levels and anti-contactin 1 IgG4 antibodies were markedly increased. The sural nerve biopsy specimen showed IgG4-positive plasma cell infiltration in the epineurium. Treatment with steroids resulted in an amelioration of functional status, improvement of nerve conduction parameters, decreased serum IgG4 levels, and negative conversion of anti-contactin1 antibody. Further studies are needed to clarify the significance of IgG4-positive plasma cell infiltration in anti-contactin 1 antibody-positive neuropathies.

The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties.

Inclusion body myositis (IBM) is an autoimmune and degenerative disorder of skeletal muscle. The B cell infiltrates in IBM muscle tissue are predominantly fully differentiated Ab-secreting plasma cells, with scarce naive or memory B cells. The role of this infiltrate in the disease pathology is not well understood. To better define the humoral response in IBM, we used adaptive immune receptor repertoire sequencing, of human-derived specimens, to generate large BCR repertoire libraries from IBM muscle biopsies and compared them to those generated from dermatomyositis, polymyositis, and circulating CD27+ memory B cells, derived from healthy controls and Ab-secreting cells collected following vaccination. The repertoire properties of the IBM infiltrate included the following: clones that equaled or exceeded the highly clonal vaccine-associated Ab-secreting cell repertoire in size; reduced somatic mutation selection pressure in the CDRs and framework regions; and usage of class-switched IgG and IgA isotypes, with a minor population of IgM-expressing cells. The IBM IgM-expressing population revealed unique features, including an elevated somatic mutation frequency and distinct CDR3 physicochemical properties. These findings demonstrate that some of IBM muscle BCR repertoire characteristics are distinct from dermatomyositis and polymyositis and circulating Ag-experienced subsets, suggesting that it may form through selection by disease-specific Ags.

Histological improvement in chronic hepatitis C-autoimmune hepatitis overlap syndrome by glecaprevir and pibrentasvir.

A 60-year-old man with type-2 diabetes and chronic hepatitis C (HCV) was diagnosed with single hepatocellular carcinoma (HCC) of 67mm in the hepatic posterior right lobe. Lenvatinib 8mg was initiated but discontinued because of grade 3 liver injury. The patient continued to have prolonged liver injury and persistently high immunoglobulin G levels. Antinuclear antibody titer increased from 1:40 to 1:320. Histopathological examination of a liver biopsy specimen revealed interface hepatitis with lymphocyte and plasma cell infiltration, rosette formation, and emperipolesis, suggesting the possibility of autoimmune hepatitis (AIH). First, treatment with prednisolone was initiated; however, the response was poor. After starting glecaprevir/pibrentasvir (GLE/PIB) as direct-acting antivirals (DAA), HCV RNA rapidly disappeared, and serological liver function improved. After confirmation of sustained virological response 24, HCC recurrence was observed, and partial hepatectomy was performed. Background liver findings showed that liver parenchymal inflammation improved compared with that before DAA treatment. This is the first case of HCV-AIH overlap syndrome treated with DAA using GLE/PIB. Liver function improved within a short treatment period of 8weeks, as confirmed using serology and histology.