Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease.

BACKGROUND: In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice. AIM: To investigate the frequency of anti-islet autoantibodies in AITD patients. METHODS: Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups. RESULTS: The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups. CONCLUSION: Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Trends in Syphilis in Pregnant Women in Japan in 2016 and 2022.

Since 2012, the rate of syphilis infection has increased dramatically in high-income countries including Japan. In this study, we examined the rate of syphilis infection among pregnant women and perinatal outcomes in the syphilis-infected pregnancy in 2022 in Japan, and compared the results with those in 2016. We requested 2,005 obstetric institutes to provide information on syphilis infection in pregnant women who delivered in 2022. A total of 1,346 obstetrical facilities responded with valid information. We compared the results with those in our previous study. The prevalence of syphilis-infected pregnant women was 1/1,215. The incidence of preterm delivery, intrauterine fetal demise and congenital syphilis in surviving neonates in the syphilis-infected pregnancy were 9%, 2% and 7%, respectively. The prevalence of syphilis-infected pregnant women has increased significantly, while the incidence of congenital syphilis seems to have decreased clinically.

Expansion of Mental Health Care in Japanese Obstetric Institutes.

BACKGROUND: The Japan Association of Obstetricians and Gynecologists (JAOG) has raised awareness of the usefulness of identifying pregnant women with mental health problems and supporting them through multi-professional collaboration. We evaluated the results of questionnaire surveys on mental health care conducted in all obstetric institutes that are members of the JAOG annually. METHODS: Between 2017 and 2023, we requested all obstetric institutes (n = 2,073-2,427) that are members of the JAOG to provide information concerning mental health care for pregnant and postpartum women about the situation in December every year from 2017. Here, we evaluated the results of the questionnaire surveys. RESULTS: During the study periods, 56.9-74.8% of the 2,073-2,427 institutes responded with valid information. The percentage of obstetric institutes screening for mental health problems during pregnancy and the postpartum period increased from 54.3% and 53.7% to 87.1% and 83.8%, respectively (p < 0.01). However, the proportion of obstetric institutes able to manage pregnant women with mental disorders did not change significantly during the study period. CONCLUSION: There has been progress in the active identification of women with mental health problems during pregnancy and the postpartum period. However, the proportion of institutes managing mental disorders has not changed.

Antimicrobial Resistance for Chlamydia Trachomatis Genital Infection during Pregnancy in Japan.

The current study examined the antimicrobial resistance of Chlamydia trachomatis (CT) genital infection during pregnancy in Japan. We requested 2,146 obstetrical facilities that are members of Japan Association of Obstetricians and Gynecologists to provide information of CT screening tests and antimicrobial resistance in pregnant women between April 2020 and March 2021. The prevalence of CT genital infection in Japan was 2.1%. The antimicrobial resistance was recognized in 2.0 and 2.4% of the cases using azithromycin and clarithromycin, respectively. There were no significant differences in the antimicrobial resistance rate between the 2 analogues (P = 0.28). In Japan, azithromycin and clarithromycin have effectively treated genital CT infections during pregnancy.

Development of type 1 diabetes in a patient treated with anti-interleukin-6 receptor antibody for rheumatoid arthritis.

Interleukin-6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti-interleukin-6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73-year-old woman (HLA-DR9-DQ3 homozygote) with well-controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years-of-age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (-2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 µmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti-islet autoantibodies. This case report shows valuable insight regarding the effect of anti-interleukin-6 receptor antibody therapy on type 1 diabetes prevention.

Recent Prevalence of Human T-cell Leukemia Virus Type 1 Carrier Associated with Horizontal Transmission in Pregnant Japanese Women.

The current study was conducted to examine the number of human T-cell leukemia virus type 1 (HTLV-1) carriers and how horizontal transmission affected the prevalence of HTLV-1 carriers among pregnant Japanese women in 2019. We requested 2,214 obstetrical facilities to provide information on HTLV-1 tests for pregnant women who delivered in 2019. The estimated number of HTLV-1 carriers among pregnant Japanese women was 952. At least 10% or more of the carriers acquired HTLV-1 through horizontal transmission.

Current status of cervical cytology during pregnancy in Japan.

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.

Efficacy of omarigliptin, once-weekly dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes.

BACKGROUND: Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors (DPP-4is). Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice, data regarding its efficacy in patients with type 2 diabetes (T2D) after switching are limited. AIM: To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents. METHODS: Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is: switched from linagliptin, switched from sitagliptin, and switched from vildagliptin. During a 3-mo follow-up, the clinical parameters among these groups were assessed and compared, with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups. RESULTS: Hemoglobin A1c levels saw a significant decrease of -0.32% ± 0.41% in the add-on group (P = 0.002). However, the other groups' variables depended on the pre-switch daily DPP-4i: switched from linagliptin, -0.05% ± 0.22%; switched from sitagliptin, -0.17% ± 0.33%; and switched from vildagliptin, 0.45% ± 0.42%, which saw significant worsening (P = 0.0007). Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control (P = 0.0013). The mean and standard deviation of sensor glucose value, the mean amplitude of glycemic excursions, and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin. However, in patients switched from vildagliptin, not only did the glucose variability indices see no improvements, the mean of daily difference even underwent significant worsening. CONCLUSION: Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin, but not vildagliptin, improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients.

Correction to: Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

An amendment to this paper has been published and can be accessed via the original article.

Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

BACKGROUND: Screening of pregnant women carrying human T-lymphotropic virus type 1 (HTLV-1) has a crucial role in reducing the number of HTLV-1 carriers. A national HTLV-1 screening program for pregnant women was started in 2011 in Japan. The purpose of this study is to report on the implementation of this nationwide screening program. METHODS: This was a retrospective repeated cross-sectional study. We used datasets from surveys of HTLV-1-antibody-positive pregnant women performed by the Japan Association of Obstetricians and Gynecologists in 2011, 2013, and 2016. Outcomes for evaluation included the number of persons (pregnant women) who conducted the screening test, the number of positive persons (women) identified by these tests, and the proportion of positive persons to the number of persons (women) who conducted the tests. RESULTS: Numbers of target facilities changed yearly: 1857 in 2011, 2544 in 2013, and 2376 in 2016. The mean number of screening-test participants increased per facility, but the median increased or decreased. The mean number of positive individuals identified decreased. Multivariate analysis results revealed the number of screenings was slightly reduced yearly, although areas (Kanto and Kinki) and high volume in facility types increased. Regarding the positive rates, some areas (Hokkaido/Tohoku, Kanto, and Chugoku/Shikoku) exhibited decreases or increases by facility type. The number of western blotting (WB) implementations decreased in 2016, positive rates identified by WB decreased in 2016 in all areas, and the number of facility types increased. The number of PCR participants increased in 2016 in Kanto and Kinki, but a decrease in facility type was observed. Positive rates were decreased in all areas (except the central region) but facility types were increased. CONCLUSIONS: The nationwide screening program for HTLV-1 in Japan was almost fully implemented. However, regional variations in screening tests were observed during this implementation. Thus, some incentives are needed to encourage proper implementation across all regions.

Characterization of patients with diabetes who were incidentally found to be glutamic acid decarboxylase autoantibody-positive by bridging-type enzyme-linked immunosorbent assay.

This study aimed to characterize diabetic patients incidentally found to be positive for glutamic acid decarboxylase autoantibodies (GADA) in general practice. Using bridging-type enzyme-linked immunosorbent assay, we screened 1,040 patients with phenotypic type 2 diabetes for GADA, finding 25 (2.4%) to be positive. However, on retesting, with a median interval of 19 days, 44% of GADA-positive patients turned negative (Disappearing Group). The mean age at diabetes onset was significantly higher (P < 0.05) and GADA titers at first determination were significantly lower (P < 0.001) in the Disappearing Group compared with the Persistent Positive Group. On initial screening, all patients in the Disappearing Group had GADA titers of <6.5 U/mL. The current study showed that a portion of phenotypic type 2 diabetic patients incidentally identified as GADA-positive were falsely positive, and that to avoid the misclassification, remeasurement of GADA is essential in cases showing very low titers.

Statin-induced autoimmune hepatitis in patients with type 1 diabetes: A report of two cases and literature review.

Statins are widely used medications for the treatment of hypercholesterolemia, as well as prevention of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin. The first patient developed the marked elevation of liver enzymes 6 months into atorvastatin therapy. The second patient developed liver dysfunction 8 months after the initiation of rosuvastatin therapy. Liver biopsies in both patients showed either portal, interface and lobular hepatitis or a piece-meal necrosis with lymphocytes and plasma cell infiltration that were compatible with autoimmune hepatitis. Then, both patients were started on prednisolone, to which they responded well. Liver biopsy is to be considered for type 1 diabetes patients if there is no improvement of liver dysfunction after discontinuation of statins.

Current status of Neisseria gonorrhoeae cervicitis in pregnant women in Japan.

We evaluated the current prevalence of gonococcal cervicitis among pregnant women in institutes that either do or do not routinely screen for gonococcal infection in Japan. We requested 2,330 obstetrical facilities to provide information on Neisseria gonorrhoeae cervicitis in pregnant women. A total of 1,876 (80.5%) of them responded. The universal screening test for gonococcal cervicitis, involving nucleic acid amplification for all pregnant women, was performed in 281 institutes (13.9% of institutes across Japan). The total rate of pregnant women with gonococcal cervicitis was 1.3% in the institutes performing the screening test during pregnancy, while it was only 0.2% (p < 0.01) in those not performing it. This suggests that 84% of infected women may have been missed in the institutes that do not routinely perform the screening test for gonococcal cervicitis. It may be time to examine the cost-effectiveness of providing gonococcal screening for all pregnant women in Japan.

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme-linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity.

AIM/INTRODUCTION: Autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) are a valuable diagnostic and predictive marker for type 1 diabetes. Recently, it has been reported that a significant proportion of sera in the commercial RSR radioimmunoassay (RIA) that have tested positive for GADA have then turned negative in RSR enzyme-linked immunosorbent assay (ELISA) tests in patients with type 1 diabetes. The present study aimed to investigate whether the GADA result discrepancies between RSR-RIA and RSR-ELISA are related to autoantibody affinity. METHODS: GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 in 12 discordant samples (5 RIA[+]/ELISA[-] and 7 RIA[-]/ELISA[+] sera). Furthermore, the effect of the initial incubation time on the GADA positivity was also examined using the ELISA test. RESULTS: GADA affinities were >1010  L/mol in two of five RIA(+)/ELISA(-) and all of seven RIA(-)/ELISA(+) sera. After an initial incubation time longer than the recommended 1 h, the GADA titer in three of five RIA(+)/ELISA(-) sera and all RIA(-)/ELISA(+) sera increased 1.6- to 100-fold. However, the titer in 12 GADA-negative sera from healthy controls remained unchanged after the longer incubation. The increment ratio of GADA titer was positively correlated with GADA affinity (r = 0.991, P < 0.001). CONCLUSIONS: The RSR-RIA test identifies both high- and low-affinity GADA, whereas the RSR-ELISA test identifies only high-affinity GADA. A longer initial incubation time in the RSR-ELISA test increases the sensitivity of GADA with the same specificity in patients with type 1 diabetes.

Development of Lobular Panniculitis Long After Completing the Personalized Peptide Vaccine Therapy.

BACKGROUND Personalized peptide vaccine therapy is regarded as a well-tolerated, safe and effective immunotherapy for patients with advanced cancers. Herein we report an exceptional case of a patient with advanced pancreatic cancer who developed delayed lobular panniculitis at sites corresponding to vaccine injections. CASE REPORT A 64-year-old Japanese female visited our clinic due to thirst and polydipsia; she was diagnosed as having type 2 diabetes. Simultaneously, she was diagnosed as having advanced pancreatic cancer; and a distal pancreatectomy and splenectomy were performed. Afterwards, she received adjuvant chemotherapy with titanium silicate-1 and personalized peptide vaccination using Montanide® ISA-51 by a subcutaneous injection to her abdomen over a total of 30 times. Thirteen months after the vaccine therapy had come to an end, lobular panniculitis appeared at the vaccination sites. At this point, corticosteroid was administered, resulting in significant improvement in the condition of the subcutaneous nodules. CONCLUSIONS This case report highlights the importance of careful patient explanation before initiation of cancer vaccine therapy about the possibilities of lobular panniculitis as an adverse event. It also highlights that it is important that physicians have a greater awareness of the possibility of panniculitis in patients with concerns regarding subcutaneous indurations even long after the end of peptide vaccine therapy.