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AbstractObjectiveMethodsResultsConclusionTo evaluate efficacy and safety of lebrikizumab combined with topical corticosteroids (TCS) in Japanese patients with moderate-to-severe atopic dermatitis (AD).Phase 3, randomized, double-blind, placebo-controlled study (ADhere-J; NCT04760314) conducted at 37 centers in Japan (March 2021–February 2023), comprising 16-week induction (reported herein) and 52-week maintenance periods. Overall, 286 patients aged ≥12 years and ≥40 kg were randomized (interactive web response system) to subcutaneous placebo, lebrikizumab 250 mg every 4 weeks (Q4W), or lebrikizumab 250 mg every 2 weeks (Q2W) with TCS (82, 81, and 123 patients, respectively). Coprimary endpoints were proportions of patients achieving (1) Investigator’s Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and (2) ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75) at week 16.At week 16, compared with placebo, a significantly greater proportion of the lebrikizumab Q4W and Q2W groups achieved IGA (0,1) (6.1% vs. 29.1% and 33.4%, respectively; both p < 0.001) and EASI 75 (13.4% vs. 47.2% and 51.2%, respectively; both p < 0.001). Serious adverse events (AEs) occurred in 2.4%, 0%, and 0.8% of placebo, lebrikizumab Q4W and Q2W groups, respectively. Common treatment-emergent AEs, including pyrexia (placebo: 15.9%; lebrikizumab Q4W/Q2W: 18.5%/20.3%), conjunctivitis allergic (placebo: 4.9%; lebrikizumab Q4W/Q2W: 12.3%/17.1%), and conjunctivitis (placebo: 2.4%; lebrikizumab Q4W/Q2W: 6.2%/9.8%), were more frequent with lebrikizumab; most were mild or moderate.Consistent with global data, lebrikizumab demonstrated clinical improvements with a positive benefit-risk profile in Japanese adults and adolescents with moderate-to-severe AD through 16 weeks. [ABSTRACT FROM AUTHOR]

This study holistically examined the effects of long-haul transmeridian travel (LHTT) on physiological, perceptual, sleep and performance markers in nine international level swimmers preparing for the 2019 FINA World Long Course Championships in Gwangju, South Korea. Baseline (BL) measurements were taken over two days during the week before a long-haul eastward flight across eight time-zones. Following the flight, measurements were taken over a six-day holding camp in Japan (C1-C6), and over four days at the competition venue in Gwangju before the Championships commenced (PR1-PR4). Salivary cortisol (sCort), immunoglobulin A (sIgA), alpha-amylase (sAA) concentrations and perceptual measures via the Liverpool John Moore's University Jetlag Questionnaire were assessed. Sleep was monitored using wrist activity monitors and self-report sleep diaries. Performance was assessed via squat jump (SJ), countermovement jump (CMJ) and a 4 × 100 m swim test. Participants perceived themselves to be significantly more fatigued and jet lagged than BL for five- and nine-days post-travel, respectively. Morning sCort decreased by 70% on C1 and remained significantly lower than BL until C6 (p < 0.05). Sleep ratings improved significantly in comparison to BL from C5 onwards (p < 0.05). Compared with BL, there was no significant change in swim performance or SJ height following travel; however, there was a 3.8 cm improvement (p < 0.001) in CMJ height on C5. It took ten days for elite swimmers to perceive themselves recovered from jet lag following LHTT in an eastward direction across eight time-zones. LHTT did not negatively affect sleep or physical performance in the swimmers in comparison to BL. [ABSTRACT FROM AUTHOR]

While the COVID‐19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses a threat to public health as the number of cases and COVID‐19‐related deaths are increasing worldwide, the incidence of the virus infection is extremely low in Japan compared with many other countries. To explain this uncommon phenomenon, we investigated the prevalence of naturally occurring ("natural") antibodies, focusing on those of the secretory immunoglobulin A (sIgA) form, reactive with SARS‐CoV‐2 among Japanese people. One hundred and eighty healthy Japanese volunteers of a wide range of age who had been considered to be unexposed to SARS‐CoV‐2 participated in this study. Saliva samples and blood samples were collected from all of the 180 participants and 139 adults (aged ≥ 20 years) included therein, respectively. The determination of saliva IgA antibodies, mostly comprising sIgA antibodies, as well as serum IgA and immunoglobulin G antibodies, reactive with the receptor binding domain of the SARS‐CoV‐2 spike‐1 subunit proteins was conducted using an enzyme‐linked immunosorbent assay. The major findings were that 52.78% (95% confidence interval, 45.21%–60.25%) of the individuals who had not been exposed to SARS‐CoV‐2 were positive for saliva IgA antibodies with a wide range of levels between 0.002 and 3.272 ng/mL, and that there may be a negative trend in positivity for the antibodies according to age. As we had expected, a frequent occurrence of assumable "natural" sIgA antibodies reactive with SARS‐CoV‐2 among the studied Japanese participant population was observed. [ABSTRACT FROM AUTHOR]

Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood. This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles. The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels. The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins. [ABSTRACT FROM AUTHOR]

MucoRice-CTB is a promising cold-chain-free oral cholera vaccine candidate. Here, we report a double-blind, randomized, placebo-controlled, phase I study conducted in the USA in which vaccination with the 6-g dose of MucoRice-CTB induced cross-reactive antigen-specific antibodies against the B subunit of cholera toxin (CTB) and enterotoxigenic Escherichia coli heat-labile enterotoxin without inducing serious adverse events. This dosage was acceptably safe and tolerable in healthy men and women. In addition, it induced a CTB-specific IgA response in the saliva of two of the nine treated subjects; in one subject, the immunological kinetics of the salivary IgA were similar to those of the serum CTB-specific IgA. Antibodies from three of the five responders to the vaccine prevented CTB from binding its GM1 ganglioside receptor. These results are consistent with those of the phase I study in Japan, suggesting that oral MucoRice-CTB induces neutralizing antibodies against diarrheal toxins regardless of ethnicity. [ABSTRACT FROM AUTHOR]

Background: We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleoprotein (N), spike 1 subunit (S1), and receptor‐binding domain (RBD), and neutralizing antibodies (NAbs) against SARS‐CoV‐2 in patients with coronavirus disease 2019 (COVID‐19) to understand the humoral immunity in COVID‐19 patients for developing drugs and vaccines for COVID‐19. Methods: A total of five confirmed COVID‐19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS‐CoV‐2 N, S1, and RBD and NAbs against SARS‐CoV‐2 in COVID‐19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset. Results: IgG levels against SARS‐CoV‐2 structural proteins increased over time in all cases but IgM and IgA levels against SARS‐CoV‐2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA increasing before IgG and IgM in some cases. The NAb levels were more than cut‐off value in 4/5 COVID‐19 patients some of whose antibodies against RBD did not exceed the cut‐off value in the early stage. Furthermore, NAb levels against SARS‐CoV‐2 increased and kept above cut‐off value more than around 70 days after symptom onset in all cases. Conclusion: Our findings indicate COVID‐19 patients should be examined for IgG, IgA, and IgM against SARS‐CoV‐2 structural proteins and NAbs against SARS‐CoV‐2 to analyze the diversity of patients' immune mechanisms. [ABSTRACT FROM AUTHOR]

Aim: Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti‐HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti‐HEV antibodies from a chronic hepatitis E patient. Methods: Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti‐HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near‐full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. Results: Alterations of anti‐HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. Conclusions: Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations. [ABSTRACT FROM AUTHOR]

Objective: Tonsillectomy combined with steroid-pulse therapy is a widely accepted method for the treatment of IgA nephropathy (IgAN) in Japan. However, the indication of tonsillectomy for IgAN is still controversial, and the timing of tonsillectomy is not clearly defined for the protocol of this therapy. Based on the results of a randomized control trial in Japan, the Evidence-Based Clinical Practice Guidelines for IgA nephropathy 2014 (edited in Japan) recommended tonsillectomy combined with steroid-pulse therapy for Grade C1. However, this is not widely accepted worldwide. To clarify the validity and timing of tonsillectomy, we evaluated how the three-consecutive steroid-pulse therapy method affects the tonsil tissues of IgAN patients.Methods: We examined tonsil specimens from 35 IgAN patients and 8 chronic tonsillitis patients. We compared the proportion of follicular area to total tonsillar area and the number of germinal centers between each group on hematoxylin and eosin stained pathological specimens to clarify the histopathological characteristics of tonsils from IgAN patients. Based on these findings, we examined the tonsils of patients after three-consecutive steroid-pulse therapy treatments (n=34) to determine the influence of this therapy on the tonsil tissues of IgAN patients. Moreover, we observed chronological changes in tonsil tissues after steroid-pulse therapy.Results: The extrafollicular area was enlarged in IgAN patients before steroid-pulse therapy compared with chronic tonsillitis patients. Just after steroid-pulse therapy, the follicles became very small with blurry outlines, and the number of germinal centers was remarkably decreased. With a gradual decrease in oral prednisolone, the tonsil tissue structure was gradually restored.Conclusion: Tonsillectomy combined with steroid-pulse therapy is considered a reasonable treatment for IgAN. Steroid-pulse therapy-induced histological changes in tonsils were transient, indicating tonsillectomy should be performed before or just after steroid-pulse therapy. [ABSTRACT FROM AUTHOR]

Background: The Japan Renal Biopsy Registry (J-RBR), a nationwide, web-based, registry system, started in 2007. This study aimed to summarise the epidemiology of biopsy-diagnosed kidney disease in Japan over 10 years., Methods: We analysed the J-RBR database, from 2007 to 2017. Patients' clinical data collected at the time of biopsy and histopathological diagnoses were used for epidemiological and clinicopathologic analyses., Results: The predominant renal biopsy diagnoses were immunoglobulin A nephropathy (39.2%), lupus nephritis (6.5%) and minimal change disease (6.0%) in younger adults (19-64 years), and membranous nephropathy (17.4%), antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis (13.0%), and immunoglobulin A nephropathy (12.5%) in older adults (≥ 65 years). The percentages of patients diagnosed with membranoproliferative glomerulonephritis and immunoglobulin A nephropathy decreased, whereas those with immunoglobulin A vasculitis and diabetic nephropathy increased over the decade. In paediatric patients (< 19 years), immunoglobulin A nephropathy (36.1%), minimal change disease (17.6%), and immunoglobulin A vasculitis (8.6%) were the predominant diagnoses. The percentage of patients diagnosed with immunoglobulin A vasculitis increased over the decade. Based on the sex distribution, minimal change disease and membranous nephropathy were predominant in men aged < 20 and > 40 years, respectively, whereas immunoglobulin A vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis were predominant in women in their 20s and 30s and aged < 50 years, respectively. Immunoglobulin A nephropathy was predominant in men at most ages and in women in their 20s to 40s., Conclusions: This study describes the distribution and changes in kidney biopsy diagnoses over 10 years in Japan and paves the way for future research on kidney diseases in adults and children., (© 2023. The Author(s).)

Background/purpose: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors., Methods: We recruited 58 patients with PSC (mean age; 37.4 years, mean observation period; 1382 days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY)., Results: The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival., Conclusions: High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis., (© 2023. The Author(s).)

This study aimed to calibrate hepatitis E virus (HEV) serological assays. We optimized the previously developed in-house HEV antibody enzyme-linked immunosorbent assay (ELISA) by setting the cutoff with an in-house serological performance panel consisting of broad HEV antibody titers and subtracting nonspecific background values for anti-HEV IgM, IgA, and IgG. We also compared the assay's performance with that of commercial serological assay kits (four kits for IgM, one for IgA, and two for IgG). Although all serological assays readily detected HEV antibodies at high titers in the symptomatic hepatitis E population, considerable variations between assays were observed in the asymptomatic population. The in-house ELISA showed a higher sensitivity for HEV IgM, IgA, and IgG than the commercial kits and detected the seroconversion of HEV IgM and IgG earlier when testing a commercially available HEV seroconversion panel. The low sensitivity of the commercial kits was due to the high setting of the original cutoff, which was demonstrated by receiver operating characteristic analysis. However, the corrected cutoff value reduced assay specificity. Background subtraction is essential to achieve high specificity because the in-house ELISA without background subtraction reduced its specificity. These results indicate that asymptomatic specimens and background subtraction contribute to the optimization of HEV serological assays. IMPORTANCE Accurate diagnosis of hepatitis E virus (HEV) infection is essential for public health surveillance and for preventing HEV-contaminated blood transfusion. Anti-HEV IgM or IgA is used as a reliable marker of recent HEV infection. However, considerable variability in the sensitivity and specificity of HEV antibody detection is observed among several commercially available assay kits. In addition, none of the HEV antibody detection methods have been approved by the U.S. Food and Drug Administration (FDA). Here, we show that the in-house enzyme-linked immunosorbent assay (ELISA) could detect HEV IgM and IgA more sensitively than commercial kits in the asymptomatic population. We also suggest that the assay performance of commercial kits might be improved by optimizing the cutoff and reducing nonspecific background noise. A sensitive serological (IgM or IgA) assay in addition to HEV RNA testing will contribute to accurate diagnosis of acute HEV infection because HEV RNA-positive duration is relatively short.

Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted. [ABSTRACT FROM AUTHOR]

We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. Themean age at onset was 43.8, and 13 years earlier for female patients.More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients. [ABSTRACT FROM AUTHOR]

Background: The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007. Methods: The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008. Results: Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%). Conclusions: In a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR. [ABSTRACT FROM AUTHOR]

Aim of the study: Red Ginseng roots (Panax ginseng C.A. Meyer) have traditionally been thought to have anti-allergic effects, but their influence on food-induced allergic responses is unclear. Materials and methods: This study examined the effects of a Red Ginseng extract on an ova-albumin (OVA)-evoked allergic reaction in mice. Results and conclusions: The orally administered extract significantly inhibited the increase in OVA-specific IgG1 (Th2) levels in OVA-sensitized mice, but had no effect on OVA-specific IgE (Th2) levels. The extract prevented a reduction in IL-12 production and the ratio of IFN-γ (Th1) to IL-4 (Th2) in splenocytes, and enhanced small intestinal CD8-, IFN-γ-, and IgA-positive cell numbers in the OVA-sensitized mice. These findings suggest that Red Ginseng inhibits allergic reactions to food by preventing reductions in the ratio of IFN-γ to IL-4 and in IL-12 production induced by dietary antigens in spleen cells, and/or increasing the expression of CD8 and IFN-γ in the small intestine. It may also protect against sensitization to antigens as an immunomodulator by increasing intestinal IgA secretion without affecting antigen-specific IgE levels. In conclusion, Red Ginseng roots may be a natural preventative of food allergies. [Copyright &y& Elsevier]

Background: Evaluating the frequency of renal disease according to sex, age, time period and ethnicity is of considerable importance. Methods: Disease frequency was evaluated in a total of 2,404 cases that had undergone a renal biopsy at Tokyo Women’s Medical University between 1979 and 2008. Results: The overall frequencies of primary glomerulonephritis (GN) and secondary GN were 77.8 and 14.4%, respectively. Primary GN and nephrosclerosis occurred more frequently among men, while secondary GN was more frequent among women. Primary GN decreased and secondary GN increased with advancing age. Immunoglobulin A nephropathy was the most common form of primary GN during each time period and also gradually increased over time (44.4–57.4%). The most common form of secondary GN was lupus nephritis (59.0%); this disease was commonly observed in women (79.3%) but not as frequently among men (27.9%). Our data regarding the frequencies of each form of primary GN were almost the same as data from other regions of Japan and East Asia but were quite different from data originating in West Asia and South America. Conclusions: Our epidemiological results may be useful for analyzing the morbidity of renal disease. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Immunoglobulin (Ig)A nephropathy is one of the major causes of chronic kidney disease (CKD) in Japan. Despite statutory urinalysis of industrial workers and school children, Japan unfortunately still ranks among the countries with the highest CKD-5D prevalence in the world. Topics of this review are as follow: (i) early diagnosis and treatment; (ii) influence of the period from onset to medical intervention on renal prognosis; and (iii) epidemiology of IgA nephropathy patients in Japan. Some investigators have discussed the possibility of predicting the diagnosis and prognosis of this disease. We indicated that the frequency of various casts in urinary sediments and total numbers of each type of urinary cast should provide highly convincing data for prediction of the prognosis in IgA nephropathy patients prior to renal biopsy. Furthermore, early medical intervention (anti-platelet agents, anticoagulants, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, corticosteroids and/or tonsillectomy) may lead to better renal prognosis in patients with IgA nephropathy. In a nationwide survey on IgA nephropathy in Japan, predictive factors after 10 years were as follows: (i) male sex; (ii) under 30 years old; (iii) diastolic hypertension; (iv) heavy proteinuria; (v) mild haematuria; (vi) low serum albumin; and (vii) elevated serum creatinine and impaired renal pathology. It appears that substantial renal deterioration can be validly estimated using these predictive factors in patients with IgA nephropathy. In conclusion, early diagnosis, treatment and improvement of predictive factors for a long duration may lead to better renal prognosis in patients with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) nephropathy progresses without apparent signs. The only available means of knowing the precise incidence of this disease in children is to analyze data from the school urinary screening system. Students between 6 and 15 years old with IgA nephropathy detected by school urinary screening from 1983 to 1999 in Yonago City, Japan, were examined. In addition, two hospitals with pediatric care units administered a questionnaire and patients with pediatric IgA nephropathy detected by means other than the school urinary screening program were recruited. Of 270,902 children examined by the school urinary screening system, 29 demonstrated suspected chronic nephritis on the basis of abnormal urinalysis and underwent renal biopsy procedures. Among the 29 children, 14 cases of IgA nephropathy were confirmed. During the same period, of the children examined by means other than the school screening program, 20 demonstrated suspected renal disease and underwent renal biopsies. Among these 20 children, 6 cases of IgA nephropathy were diagnosed. In all, 20 cases of pediatric IgA nephropathy were detected over the past 17 years. The incidence rate of pediatric IgA nephropathy was 4.5 cases/year per 100,000 children under 15 years. The incidence of pediatric IgA nephropathy is higher than that of idiopathic nephrotic syndrome. [ABSTRACT FROM AUTHOR]

In 1995, clinical guidelines for the diagnosis and treatment of patients with immunoglobulin A (IgA) nephropathy in Japan were published by a joint committee of the Special Study Group on Progressive Glomerular Disease, Ministry of Health and Welfare of Japan (Chairman, Kiyoshi Kurokawa, MD), and the Japanese Society of Nephrology (President, Toshihiko Nagasawa, MD).1 The purpose of this new committee of the Special Study Group on Progressive Glomerular Disease, Ministry of Health and Welfare of Japan (Chairman, Hideto Sakai, MD), is to provide new clinical guidelines for the diagnosis and treatment of patients with IgA nephropathy in Japan. Although this document addresses current clinical practice in Japan, it is hoped that this English version will be helpful to the international community and will facilitate further discussion on this increasingly important disease. [ABSTRACT FROM AUTHOR]

Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Background. Mesangial immunoglobulin A (IgA) deposition is incidentally encountered in asymptomatic individuals, but its precise frequency and significance had not been clarified. The background of the latent IgA deposition is related to the epidemiology and pathogenesis of IgA nephropathy. Methods. Zero-hour allograft biopsies were performed in 510 renal transplantations (446 living donors, and 64 cadaveric donors) at the Kidney Center of Tokyo Women's Medical University. Mesangial IgA and C3 deposition were analyzed immunohistochemically, and the frequency and clinicopathologic features of mesangial IgA deposition were investigated. Results. Mesangial IgA deposition was present in 82 (16.1%) of the total 510 allografts with no statistical difference between living donors (72/446, 16.1%) and cadaveric donors (10/64, 15.6%) or between blood-related donors (66/392, 16.8%) and nonblood-related donors (16/110, 14.5%). Mesangial C3 deposition was present in 16 (19.5%) of the 82 allografts with mesangial IgA deposition. The grade of hematuria in IgA(+) donors was significantly higher than IgA(-) donors (1.30 ± 1.17 vs. 0.86 ± 0.89, P = 0.025). Histologic investigation of IgA(+) allografts revealed the frequency of mesangioproliferative glomerulonephritis (PGN) was significantly higher in IgA(+)/C3(+) allografts (8/16, 50%) than in IgA(+)/C3(-) allografts (11/66, 16.7%) (P = 0.0084). Moreover, the number of infiltrated macrophages to glomerulus (cells/glomerular cross section) was significantly higher in the IgA(+)/C3(+) allografts than in IgA(+)/C3(-), IgA(-)/C3(+) and IgA(-)/C3(-) allografts (1.10 ± 0.62 vs. 0.61 ± 0.42, P = 0.0008; 0.47 ± 0.34, P = 0.023; and 0.37 ± 0.23, P = 0.002, respectively). Conclusion. The latent mesangial IgA deposition was a relatively common phenomenon in the healthy Japanese donors. This phenomenon was associated with mild degree of microhematuria, mesangial proliferation and glomerular macrophage infiltration in some of the affected individuals, especially with combined IgA and C3 deposition. [ABSTRACT FROM AUTHOR]

Pemphigoid nodularis is a rare variant of bullous pemphigoid. We report a 49-year-old Japanese male with clinical and histopathological features of pemphigoid nodularis including circulating and in vivo-bound IgG antibasement membrane zone antibodies and IgA anti-intercellular antibodies. Although the precise molecular target of the IgG autoantibodies could not be determined, intriguingly, immunoblotting showed that the IgA in the patient’s serum reacted with the intracellular domain of desmoglein 1, the target antigen in cases of pemphigus foliaceus. However, the IgA did not react with the extracellular domain of desmoglein 1 in sensitive enzyme-linked immunosorbent assay studies using a baculovirus system. These results suggest therefore that these IgA antibodies may possibly not be pathogenic. The mechanism for the production of different autoantibodies is unknown, but this case provides further illustration of the atypical skin immunoreactants often seen in this unusual subtype of bullous pemphigoid. [ABSTRACT FROM AUTHOR]

Colostrum is the first food for newborns and it contains various crucial immune factors. The concentrations of immune factors in breast milk may change depending on maternal characteristics such as body mass index, collection day, and age at first pregnancy. In this exploratory study, we investigated the association between TGF-β1, TGF-β2, and IgA in colostrum and rarely studied factors that affect breast milk components, including the use of labor-inducing medication, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. Breast milk samples were collected from 42 mothers and analyzed for TGF-β1, TGF-β2, and IgA. The results suggest that parity and mode of delivery may be correlated with the concentrations of immune factors in colostrum. However, we found no association between the immune factors in colostrum and the use of labor-inducing medications, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. These findings have some implications for further analysis of the effects of immune factors in breast milk on the prognosis of allergies in children.

Immunoglobulin A (IgA) vasculitis is a systemic small-vessel vasculitis involving the skin, kidney, joints, and gastrointestinal tract. Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by periodic fever, peritonitis, pleuritis, or arthritis. It is well known that FMF may coexist with vasculitis, especially small and medium vessel vasculitis. Here we present a Japanese male patient with FMF who later developed IgA vasculitis and a relapsing disease course. A 51-year-old Japanese male was referred because of upper abdominal pain, arthralgia, and bilateral purpura of the lower limbs. He fulfilled the criteria for IgA vasculitis, which was successfully treated by corticosteroid and immunosuppressive therapy. He had a medical history of periodic fever since the age of 10 years old. The Mediterranean fever (MEFV) gene analysis revealed that he was heterozygous for M694I and E148Q mutations. Colchicine therapy resolved his periodic febrile attacks. To our knowledge, coexistence of FMF with IgA vasculitis has not been reported in East Asia, including Japan. Our case suggests that MEFV gene exon 10 mutations could be related to the development of IgA vasculitis and affects its clinical course.

Objective Immunoglobulin (Ig) A vasculitis (IgAV) is a systemic vasculitis characterized by purpura and gastrointestinal involvement showing abdominal pain that usually occurs after the emergence of purpura. Criteria for evaluating gastrointestinal manifestations of IgAV are unavailable at present, so we conducted a study to investigate the usefulness of video capsule endoscopy (VCE) for detecting gastrointestinal manifestations of IgAV. Methods The clinical data of 10 patients who underwent VCE for IgAV at our hospital from 2012 to 2017 were collected. Nine patients underwent esophagogastroduodenoscopy, and five underwent colonoscopy. We compared the endoscopic severity determined by VCE to the findings of esophagogastroduodenoscopy and colonoscopy. Results The rates of positive findings of esophagogastroduodenoscopy, VCE, and colonoscopy were 56%, 100%, and 80%, respectively. In 70% of cases, the most severe gastrointestinal findings were detected by VCE. VCE was performed on average 16.8 days after the emergence of purpura, and in 8 of 10 patients, its result triggered the initiation of steroid therapy or the control of the steroid dose. Conclusion VCE is very useful for confirming gastrointestinal involvement in IgAV and may be used to determine the timing of steroid therapy initiation. We recommend performing VCE when IgAV is suspected in patients with gastrointestinal symptoms.

Objective This case series aimed to identify the clinical and pathological characteristics of elderly patients (≥60 years) with biopsy-proven IgA vasculitis with nephritis (IgAVN). Methods The clinical and pathological presentation and treatment outcomes were compared between two groups. Patients Patients with IgAVN who were ≥19 years old at the time of their renal biopsy were divided into elderly (≥60 years) and adult (19-59 years) groups. Results Of the 23 patients in our study, 13 were elderly. In the elderly group, the median age at the diagnosis was 68 years (range, 60-85 years), with a median follow-up period of 15 months (range, 3-80 months). Twelve elderly patients had comorbidities, including hypertension, diabetes mellitus, chronic kidney disease, cardiovascular disease, and malignancies. A decrease in the estimated glomerular filtration rate, as well as massive proteinuria and rapidly progressive nephritic syndrome, were more frequent in the elderly group than in the adult group. Furthermore, renal pathological changes, including cellular or fibrocellular crescents, interstitial fibrosis, tubular atrophy, and arteriosclerosis, were more severe among elderly patients than adult patients. All elderly patients were treated with glucocorticoids and had no incidence of end-stage renal disease at the final follow-up; in addition, nine elderly patients had reduced proteinuria with a preserved renal function. Adverse events, including infection, diabetes mellitus, and vascular disorders, were identified in nine patients. Three elderly patients died from severe infections. Conclusion IgAVN in elderly patients is characterized by severe renal involvement. Elderly patients are at higher risk than adults for treatment-related adverse events.

Describes the immunological and clinical features of the first case of Crohn's disease associated with selective Immunoglobulin A deficiency in Japan. Observance of longitudinal ulcers and aphthoid lesions between the terminal ileum and the sigmoid colon; Administration of metronidazole; Effectiveness of metronidazole and ciprofloxacin in the inflammatory lesions.

Chronic obstructive pulmonary disease (COPD) is a possible risk factor for cardiovascular disease. The association of COPD with the pathogenicity of infection with Chlamydia pneumoniae and Mycoplasma pneumoniae is controversial. We conducted a cross-sectional study to clarify the association between atypical pneumoniae seropositivity and COPD in a general population. We also investigated genetic polymorphisms conferring susceptibility to a pneumonia titer. The study included 9040 Japanese subjects (54 ± 13 years). COPD was defined as a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 70%. Serum levels of IgA and IgG antibodies to C pneumoniae were determined using an enzyme-linked immunoassay, and M pneumoniae seropositivity was assessed by a particle agglutination test. Subjects seropositive for C pneumoniae (26.1%) had a higher prevalence of COPD (seropositive, 5.8%; seronegative, 3.1%; P < 0.001) after adjustment for age, sex, height, weight, and smoking status. The association between M pneumoniae seropositivity (20.4%) and COPD was also significant in covariate-adjusted analysis (P < 0.001). A genome-wide association analysis of the C pneumoniae IgA index identified a susceptible genotype (rs17634369) near the IKZF1 gene, and the seropositive rate of C pneumoniae significantly differed among genotypes (AA, 22.5; AG, 25.3; GG, 29.7%, P < 0.001). On multiple regression analysis, seropositivity for both C pneumoniae (odds ratio = 1.41, P = 0.004) and M pneumoniae (odds ratio = 1.60, P = 0.002) was an independent determinant for COPD, while no direct association was found with the rs17634369 genotype. Seropositivity for both C pneumoniae and M pneumoniae is an independent risk factor for COPD in the general population.

The ELNAS Plate Chlamydophila pneumoniae commercial test kit for the detection of anti-C. pneumoniae-specific immunoglobulin M (IgM), IgA and IgG antibodies has become available in Japan recently. To determine the optimum serum collection point for the ELNAS plate in the diagnosis of C. pneumoniae pneumonia, we analyzed the kinetics of the antibody response in patients with laboratory-confirmed C. pneumoniae pneumonia. We enrolled five C. pneumoniae pneumonia cases and collected sera from patients for several months. The kinetics of the IgM and IgG antibody responses were similar among the five patients. Significant increases in IgM and IgG antibody titer between paired sera were observed in all patients. IgM antibodies appeared approximately 2-3 weeks after the onset of illness, reached a peak after 4-5 weeks, and were generally undetectable after 3-5 months. IgG antibodies developed slowly for the first 30 days and reached a plateau approximately 3-4 months after the onset of illness. The kinetics of IgA antibody responses were different among the five patients, and significant increases in IgA antibody titer between paired sera were observed in only two patients. Although the sample size was small, the best serum collection time seemed to be approximately 3-6 weeks after onset of illness when using a single serum sample for the detection of IgM antibodies. Paired sera samples should be obtained at least 4 weeks apart. IgA antibody analysis using ELNAS may not be a useful marker for acute C. pneumoniae pneumonia., (Copyright © 2015. Published by Elsevier Ltd.)

The article focuses on the genetic mapping of familial immunoglobulin A (IgA) nephropathy (IgAN). IgAN is the most common form of glomerulonephritis and a principal cause of end-stage renal disease. Numerous familial cases have been reported, suggesting that a substantial fraction of patients have genetic predisposition. Despite higher incidence of IgAN in Japan and other Asian countries, the genetic factors underlying IgAN in Japan remains to be investigated. The analysis to evaluate the statistical power of a family was done.

Focuses on the medical history and lifestyle risk factors for immunoglobulin A (IgA) nephropathy in Japan. Conditions found to be protective against IgA nephropathy.

We report 10 Japanese patients with Sjögren's syndrome (SS) who developed monoclonal gammopathies (MG). One was of the IgG class, five of IgA, three of IgM, and one of IgG/IgM. The monoclonality of 7 of 10 M proteins was studied using antiidiotypic (Id) antibodies against M proteins. Four (three IgA and one IgM) of 10 M proteins had rheumatoid factor (RF) activity. Hemagglutination inhibition tests and enzyme-linked immunosorbent assays (ELISA) showed that the RF activity was inhibited by anti-Id antibodies in all four monoclonal RFs. In two patients examined, many cells infiltrating into the salivary glands were stained with anti-Id antibodies. Our review of 19 Japanese SS patients with MG revealed that the non-IgM class predominated (13/19). This contrasts with 19 reported non-Japanese SS patients, among whom 14 were IgM. In both Japanese and non-Japanese patients there was a higher incidence of MG in primary than in secondary SS. The difference in the dominant heavy-chain class may reflect a difference in the genetic factors affecting B cell differentiation in immunologically disordered states.

Myasthenia gravis, malignant thymoma, multiple schwannomas and monoclonal IgA gammopathy coexisted in a 54-year-old Japanese man. Serum acetylcholine receptor antibody activity was located in the IgG fraction, but not in the paraprotein peak. It was speculated that all these disorders might fall under the spectrum of the diseases associated with thymic abnormality or that some growth factors might induce neoplasms and activation of B cell clones of autoantibodies (including acetylcholine receptor antibody) in this case.