Immunological Tests Research Articles

Igg4 Related Granulomatous Spinal Pachymeningitis with Cord Compression – A Multisystem Disorder Presenting as Tumor Mimic

IgG4 Related Disease (IgG4 RD) is a comparatively new multisystem disorder associated with elevated levels of IgG4. It includes a number of disorders which were previously thought to be idiopathic or autoimmune. This is a rare condition and can affect any organ system in the body with IgG4 Related pachymeningitis having even lesser incidence. In this case report we present a patient who had chronic low back ache, who on evaluation was found to have a mass compressing on the spinal cord at the thoracic level, requiring surgical decompression. Biopsy and immunological testing were suggestive of IgG4 related pachymeningitis. We describe the diagnosis, medical management, and follow up of this patient, with discussion on how timely diagnosis and management will help in preventing further episodes and help in recovery. This case reiterates about medical conditions presenting as tumor mimics.

Targeting the Highly Conserved 3' Untranslated Region of Iris Severe Mosaic Virus for Sensitive Monitoring of the Disease Prevalence in Iris Production.

Iris severe mosaic virus (ISMV, Potyviridae) can threaten the sustainability of iris production and the marketability of the plants. Effective intervention and control strategies require rapid and early detection of viral infections. The wide range of viral symptoms, from asymptomatic to severe chlorosis of the leaves, renders diagnosis solely based on visual indicators ineffective. A nested PCR-based diagnostic assay was developed for the reliable detection of ISMV in iris leaves and in rhizomes. Considering the genetic variability of ISMV, two primer pairs were designed to detect the highly conserved 3' untranslated region (UTR) of the viral genomic RNA. The specificity of the primer pairs was confirmed against four other potyviruses. The sensitivity of detection was enhanced by one order of magnitude using diluted cDNA and a nested approach. Nested PCR facilitated detecting ISMV on field-grown samples beyond the capabilities of a currently available immunological test and in iris rhizome, which would facilitate ensuring clean stock is planted. This approach dramatically improves the detection threshold of ISMV on potentially low virus titer samples. The study provides a practical, accurate, and sensitive tool for the early detection of a deleterious virus that infects a popular ornamental and landscape plant.

Рідкісні форми ураження очей при хворобі Лайма в дітей

Lyme disease (LD) is a multisystem disease caused by Borrelia burgdorferi and other similar tick-borne borrelia. Purpose - to analyse and present clinical cases of eye lesions in children with suspected LD for differential diagnosis and treatment refinement. We present 2 clinical cases with ocular lesions in children of infectious genesis with suspected LD. Basic examinations, ophthalmoscopy, optical coherence tomography with angiography, clinical and immunological tests, including ELISA and immunoblot, were performed. Serological results were compared in children with different forms of eye lesions of infectious genesis. Conclusions. The diagnosis of LD should be confirmed by laboratory tests (ELISA and western blot serological tests), indicating the presence of specific anti Borrelia burgdorferi IgM/IgG antibodies, and confirming the clinical manifestations of the disease. Paediatricians should be alert to LD, especially in residents of endemic areas. The need for prophylactic treatment of LD in children exposed to tick bites has been proven. The diagnosis of LB in children should be laboratory confirmed by a two-step method (ELISA serological tests and western blot), which confirms the clinical manifestations of the disease. The study was performed in accordance with the principles of the Declaration of Helsinki. Informed consent of parents and child was obtained for the study. No conflict of interests was declared by the authors.

Cytomegalovirus esophagitis associated with arytenoid cyst in an immunocompetent host

CMV esophagitis is usually encountered in immunocompromised individuals and esophagus is rarely affected in immunocompetent individuals. CMV esophagitis associated with arytenoid cyst has not yet been reported in literature to the best of my knowledge and can be considered in case of recurrence of cyst following excision. The objective of this study is to report the unique presentation of CMV in an immunocompetent patient. A middle-aged immunocompetent lady presenting with dysphagia was diagnosed to have arytenoid cyst. Biopsy from upper esophagus revealed cytomegalovirus inclusion bodies and immunological test were performed to confirm the pathology. The cyst excision lead to recurrence. It was excised again followed by a course of intravenous ganciclovir. Currently, the role of antiviral in treatment of CMV esophagitis in immunocompetent individual is not well established. We have obtained good result in this patient with a course of Ganciclovir following excision of the cyst. The rarity of cytomegaloviral upper esophageal involvement, its association with arytenoid cyst and the utility of antivirus in treatment of an immunocompetent host makes this case report unique and interesting.

Possibilities of Detecting an Epidemic Focus of Tuberculosis Infection in an Indicator Patient with a Positive Immunological Test for Tuberculosis

Relevance. In connection with the advent of new diagnostic immunological tests, it became possible to determine a potential focus of infection not only through the identification of patients with tuberculosis, but also through the identification of patients infected with M. tuberculosis, who still do not have manifestations of a local form of the disease. This made it possible to search for persons who were infected with an unknown source of tuberculosis infection in order to conduct an in-depth epidemiological investigation and detect hitherto unknown foci of tuberculosis. Aims. To study the effectiveness of identifying the source of infection in the environment of a patient with a positive immunological test for tuberculosis («indicator» patient). Materials and methods. 1) A retrospective study of the data of all 30 patients with tuberculosis in the period from 2014 to 2019 in Moscow, identified by indicator patients with a positive immunological test, was carried out. 2) A cohort of patients with latent tuberculosis infection with and without HIV infection (Moscow) was studied in the period 2020–2021. to determine the prevalence of latent infection in the close circle of communication of indicator patients. Results. Patients with tuberculosis, forming hidden foci and identified by the indicator patients infected by them with a latent infection, in 56.7% of cases were not examined for tuberculosis for 2–10 years, in 50.0% they suffer from tuberculosis with registered bacterial excretion, in 46.7% of cases are internal or external migrants. The prevalence of latent tuberculosis infection among indicator patients is 10%, which is many times higher than the prevalence of latent tuberculosis infection among the permanent population of Moscow (less than 1%), in HIV-infected risk groups (up to 5%), in known foci of tuberculosis on average in Moscow (5%). The TB notification rate in the environment of indicator patients with latent tuberculosis infection is 38.8 per 100,000 of the corresponding group and exceeds that among the permanent population of Moscow by 5.4 times. Conclusion. A modified epidemiological investigation aimed at examining the environment of persons with latent TB infection among adults makes it possible to identify TB patients who have infected indicator patients and to identify other infected patients.

Noticeable immune dysregulation-and-suppression in parvovirus affected dogs

Canine parvovirus type 2 (CPV-2) is one of the most common causes of infectious diarrhea in small animals, with high mortality and morbidity. Information on the specific treatment option(s) for CPV diseases (CPVD) is unachievably little. So, the treatment is mainly supportive one. Disruption of dog's innate immune system in viral diseases simply occurs; presumably, the CPV-2 may change the level of some TLRs, interleukins, CD4 and CD8 in the leukocytes of CPVD dogs, and disruptive activities of these immune molecules might be attributable to severe CPVD in dogs. Study on the role of the key immune molecules in CPVD is rare. Herein, by conducting and relating the clinical, para-clinical, immunological and molecular diagnostic tests, we tried to establish how some key immune molecules behave in blood of parvovirus affected dogs. As such, in the 1st study, the mRNA levels of TLR2, TLR4, TLR9, IL-1β, IL-6, CD4 and CD8 genes in the leukocytes of CPVD were assessed with quantitative (q)RT-PCR along with CPV-2 detection by rapid immunochromatography and PCR tests. In a 2nd study, the same measurements as in the 1st study were evaluated in two groups of mild versus severe clinical signs of CPVD. Both in the 1st and the 2nd studies leukopenia, much more pronounced in the severe CPVD, and immune dysregulation were observed. In the 1st study, a noticeable increase in the mRNA levels of TLR2 and TLR4 was detected with a slight decrease in TLR9 and a significant decrease in the expression of IL-1β, IL-6, CD4 and CD8 in leukocytes of CPV-infected dogs. Compared to the mild CPVD, the intense of downregulating effects on those immune molecules in the 2nd study was remarkably much more pronounced in the severe CPVD. Overall, it proves strong immune dysregulation and suppression/incompetence and potential T-cells exhaustion in severely CPV-2-affected dogs. Technically and clinically, this would be substantially applicable in canine medicine. By targeting those key immune molecules and their signaling pathways, new clinicodiagnostic approaches for CPVD can be evolved, and biotechnicoclinically this would be substantially applicable in all physiopathological conditions of dogs.

Biochemical, Serological and Immunological Tests for Diagnosis of Coronavirus Disease 2019 (COVID-19) Patients: A Comprehensive Systematic Review and Meta-analysis.

Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients. This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions. Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6). The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

Issues of interdisciplinary interaction during detection and diagnosis of tuberculosis in children and adolescents: a literature review and comments

Interdisciplinary interaction between phthisiatricians and pediatricians on the issues of detection and diagnosis of tuberculosis provides basis for the reduction of duration of the diagnostic process and the early identification of disease progression. The purpose of this review and comments is to systematize the knowledge of pediatricians about the detection and diagnosis of tuberculosis in children and adolescents in primary health care (PHC) facilities to improve the diagnostic process. We have performed an analysis and systematization of the current directive and methodological documents, articles on the detection and diagnosis of tuberculosis in PHC facitlities. The significance of skin immunological tests (Mantoux test using 5 tuberculin units (TU) of purified protein derivative (PPD)-L and a test with recombinant tuberculosis allergen (RTA)) during mass and selective screening to form groups at high risk for Tuberculosis and detect the disease is emphasized. The doctor’s actions based on the current guiding documents and laws are presented for cases when parents/legal representatives or the patient himself refuses from immunological skin tests. Positions that determine the need for interdisciplinary interaction for pediatricians on the issues of detection, diagnosis and differential diagnosis of tuberculosis are clearly articulated. The pathway to diagnosis begins with the formation of groups at high risk for tuberculosis in PHC facilities and with seeking medical help from a pediatrician in the presence of clinical signs similar to those of tuberculosis. Particular attention is paid to the detection of the disease when patients with clinical symptoms similar to those of tuberculosis seek medical help, and the missed opportunities for its early diagnosis are presented. Predictors allowing pediatricians to suspect tuberculosis and promptly refer a patient to a phthisiatrician to confirm / exclude the disease are provided.

28 On-Farm Rapid Test to Assess Immunological Health of Young Pigs

Abstract Immunological competence is important for young pig survivability. A rapid on-farm test of immunological status may be a tool to help with early identification of sick animals. A new immunological test uses gold nanoparticle technology (D2Dx) to detect changes in serum proteins, particularly IgG and was evaluated as a potential on-farm measure of immunological health of pigs born during a farm level Porcine Respiratory Reproductive Syndrome (PRRS) outbreak. Up to three piglets from each litter in 2 farrowing groups (28 days apart) were selected for serial blood sampling and monitoring of body weight. Group 1 (n = 13 sows) experienced the PRRS outbreak approximately 14 days before farrowing and Group 2 (n = 15) approximately 40 days before farrowing. Attempts were made to select one piglet from each of 3 general categories [small (< 1.0 kg), average (1.1 – 1.6 kg), heavy (>1.6 kg)] from each litter. Serum samples were collected at day 2 and 15 of age from each piglet and serum IgG concentration and D2Dx ratio were assessed. Serum immunocrit at day 2 was also completed. Daily animal care of piglets and sows followed standard barn protocols. No creep feed was provided, sows were fed ad libitum, and cross-fostering was limited. Stillborn rate and preweaning death loss was approximately 70% in Group 1 and 35% in Group 2. Birth weight was similar between Group 1 and 2 litters (1.4 ± 0.3 kg). However, body weight gain to day 15 was 1.7 ± 0.95 kg and 2.7 ± 1.1 kg for piglets from Group 1 and 2, respectively, which may be due to timing of the PRRS outbreak. The D2Dx ratio declined from day 2 to 15 (0.029 vs -0.002) in both groups and was significantly reduced in Group 2 pigs (P < 0.001). A lower ratio suggests a stronger type 2 immune response and has been associated with decreased overall immunity in cattle, humans, and rodents. The D2Dx ratio was negatively correlated (r = -0.58) with BW gain in Group 1 pigs and positively correlated (r = 0.36) with gain in Group 2 pigs. Both immunocrit (day 2) and IgG (d15) were greater in Group 1 pigs than Group 2 (P < 0.01). There was a no relationship between birth weight and day 2 serum immunocrit (R2 = 0.06) or day 2 D2Dx (R2 = 0.01). There was no relationship between serum IgG and D2Dx at d15. The PRRS disease activity impacts immunocrit and serum IgG measures in the neonatal pig. The D2Dx ratio was not strongly related to piglet immunological status under disease conditions; however, the stronger type 2 immune response may be reflective of positive changes in piglet immune function and the response to maternal PRRS antibodies in milk.

Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India.

Primary immune deficiencies or inborn errors of immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoinflammation and malignancies. IEIs are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care center in South India were included in the study. The clinical features, laboratory findings including microbiologic and genetic data, and treatment and outcome details were analyzed. The diagnosis of IEI was confirmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male-to-female ratio was 1.8:1. Of the 208 patients, 72 (34.6%) were < 1yr, 112 (53.8%) were 1-18years, and 24 (11.5%) were above 18years. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a significant proportion of patients with DOCK8 deficiency (7.2%), LAD (6.2%) and six patients (2.8%) with autoinflammatory diseases. Autoimmunity was noted in forty-six (22%) patients. Molecular testing was performed in 152 patients by exome sequencing on the NGS platform, and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period, and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the profile of 208 patients with IEI, and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.

From a rat otorrhagia to a febrile rash

A 19-year-old patient, without medical history, presented a first episode of continuous fever (about 39°C) for 14 days, with rash and arthromyalgia and functional impotence of the ankles for 7 days. Clinically, the patient had asthenia with ankle biarthritis with a predominantly palm-plant rash (Figure 1). Right ankle joint puncture finding inflammatory fluid (5300 nucleated elements/mm3 including 91% neutrophils), without microcrystals. Immunological test (rheumatoid factor and citrullinated anti-peptide antibodies) was negative. The skin biopsy performed in an area of pathological skin is in favor of an infectious origin, with microabscesses.

Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis.

Immunological assays based on the detection of circulating fungal biomarkers are helpful in clinical practice for diagnosing invasive fungal infections. Some of these targeting antigenic components are common to several different fungi. Histoplasmosis is a mycosis caused by the dimorphic fungus Histoplasma capsulatum, which in recent years has gained significant relevance due to the increase in the population susceptible to developing severe clinical forms, including those living with HIV/AIDS. Immunological tests that detect cell wall polysaccharide antigens are among the most used laboratory techniques for diagnosing this mycosis. However, none have shown adequate performance, and cross-reactivity with other fungal pathogens may be observed. Considering that there is a real need to improve the sensitivity and specificity of current diagnostic methods, we explored a novel strategy for the identification of H. capsulatum-specific antigens (Hc_Ags) that could be detected in clinical samples during infection based on a computational analysis model that included the application of bioinformatics tools and the analysis of experimental data from transcriptomics and proteomics. The Hc_Ags identified were expressed and purified by eukaryotic and prokaryotic systems. First, the Hc_Ags were used in an in-house immunization model in mice (BALB/c) to obtain Hc_Ag-specific polyclonal antibodies (Hc_Ag_PAb). Then, the presence of these antigens in H. capsulatum-yeast culture extracts and the specificity of Hc_Ag_PAb against culture extracts of Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Fusarium spp., and Paracoccidioides brasiliensis were confirmed. Finally, we demonstrated the immunoreactivity of these Hc_Ag-specific polyclonal antibodies with urine samples from patients previously diagnosed with histoplasmosis.IMPORTANCEHistoplasmosis is considered one of the most important mycoses due to the increasing number of individuals susceptible to develop severe clinical forms, particularly those with HIV/AIDS or receiving immunosuppressive biological therapies, the high mortality rates reported when antifungal treatment is not initiated in a timely manner, and the limitations of conventional diagnostic methods. In this context, there is a clear need to improve the capacity of diagnostic tools to specifically detect the fungal pathogen, regardless of the patient's clinical condition or the presence of other co-infections. The proposed novel pathogen-specific biomarkers have the potential to be used in immunodiagnostic platforms and antifungal treatment monitoring in histoplasmosis. In addition, the bioinformatics strategy used in this study could be applied to identify potential diagnostic biomarkers in other models of fungal infection of public health importance.

Eccentric Contraction Enhances Healing of the Bone-Tendon Interface After Rotator Cuff Repair in Mice

Background: Various muscle contraction modalities have differing effects on the musculoskeletal system. To understand the magnitude of these effects, the authors investigated the effects of eccentric and concentric contractions on the bone-tendon interface after rotator cuff repair in mice. Hypothesis: Eccentric contraction promotes healing of the bone-tendon interface after rotator cuff repair in mice better than other muscle contraction patterns. Study Design: Controlled laboratory study. Methods: The authors performed acute supraspinatus tendon repair of the right shoulder in 104 C57BL/6 mice. Animals were randomized into 4 groups postoperatively: control group (Con group), horizontal running group (Horz group), +15° uphill running group (Up group), and −15° downhill running group (Down group), with 26 animals in each group. At 4 and 8 weeks postoperatively, the authors removed the eyeball, collected blood samples, and extracted the supraspinatus tendon–humerus complex for histological, immunological, bone morphological, and biomechanical tests. Results: At 4 and 8 weeks postoperatively, the Down group exhibited a better collagen cell arrangement and fibrocartilage layer than the other 3 groups. At 4 weeks postoperatively, anti-inflammatory macrophages (M2 macrophages) were observed at the repair site in all groups except for the Con group. At 8 weeks postoperatively, M2 macrophages were withdrawn from the tendon site in all groups. The transforming growth factor β1 concentration in the Down group was greater than that in the other 3 groups at 4 weeks postoperatively, and it was higher than that in the Con group at 8 weeks postoperatively. The bone volume fraction, number of trabeculae, and thickness of trabeculae at the repair site in the Down group, as well as the ultimate strength and failure load in the biomechanical tests, were greater than those in the other 3 groups at 8 weeks postoperatively. Conclusion: Eccentric contraction promotes healing of the bone-tendon interface after rotator cuff repair in mice better than other muscle contraction patterns. Clinical Relevance: After clinical rotator cuff repair, patients can be rehabilitated by eccentric training to speed up the functional recovery of the shoulder joint.

ТУБЕРКУЛЕЗ ОРГАНОВ ДЫХАНИЯ У ПОДРОСТКОВ ПОД «МАСКОЙ» ВНЕБОЛЬНИЧНОЙ ПНЕВМОНИИ: КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ

Absence of pathognomonic signs of tuberculosis (TB) of the respiratory system and the diversity of its clinical manifestations reduce the alertness of primary health care (PHC) physicians to this problem, which in its turn leads to belated TB diagnosis. Most often initial diagnosis is “community-acquired pneumonia” at the onset of the disease. An algorithm for interdisciplinary interaction between pediatricians and TB specialists in cases of suspected TB of the respiratory system is proposed. The reasons for untimely detection of TB and diagnostic errors in PHC units are presented using the clinical cases. Absence of suspicion of TB in the presence of its predictors (contact with a TB patient, results of skin immunological tests); development of pulmonary disease outside the season of viral infections in patients who are not included in the risk group according to their frequency and in patients from socially problematic living conditions; incorrect interpretation of the clinical and radiological picture and the course of the disease at its onset are the main reasons for late diagnosis. Conclusion: identifying TB in children and adolescents when seeking medical help is the final part of the diagnostic journey of patients, since opportunities to diagnose the disease at earlier stages of its development were missed. The results of the presented observations indicate the need for interdisciplinary interaction between pediatric physicians and TB specialists for timely diagnosis of TB.

Long-term benefits and harms of early colorectal cancer screening in German individuals with familial cancer risk.

Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit-harm trade-offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10-yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov-state-transition model was developed and used to estimate health benefits (CRC-related deaths avoided, life-years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm-benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32-36 CRC-related deaths per 1000 persons were avoided with colonoscopy and 29-34 with iFOBT screening, compared to 29-31 (colonoscopy) and 28-30 (iFOBT) CRC-related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45-65 vs no screening), four (biennial, age 35-65), six (biennial, age 30-70) and 34 (annual, age 30-54; biennial, age 55-75). Corresponding IHBRs for 10-yearly colonoscopy were four (age 55-65), 10 (age 45-65), 15 (age 35-65) and 29 (age 30-70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group.

THU376 Isotretinoin Related DKA In Type 2 Diabetes

Abstract Disclosure: N. Radovanovic: None. R.J. Comi: None. A. Crawford: None. Introduction: Isotretinoin is a well-established treatment for acne, known to have a wide variety of adverse effects including hypertriglyceridemia, decreased HDL, and, as per some reports, increased insulin resistance. Rapid worsening of underlying diabetes after treatment with isotretinoin has been described in the literature in patients with type 1 diabetes. Clinical Case: A 45-year-old man was referred to the Endocrinology clinic in February 2022 for an urgent consultation due to rapidly worsening hyperglycemia, acidosis, hypertriglyceridemia and refusal to be evaluated in ED as recommended by his PCP. He was diagnosed with pre-diabetes in April 2021 with an HgbA1c of 6.4% and instructed to make lifestyle changes. He presented 6 months later with HgbA1c of 7.3% and the diagnosis of diabetes prompted him to initiate earlier proposed lifestyle changes. He joined an online weight loss program and was very pleased to achieve a rapid weight loss of 80 lbs within 4 months. Upon initial telephone consultation with the patient, he reported feeling well and refused our recommendations to go to the ED, but agreed to come to our clinic the next day. Upon initial in-person assessment, he denied nausea, vomiting, abdominal pain, or change in mentation but reported polyuria and polydipsia worsening in the months prior. He reported being started on isotretinoin for the treatment of acne 4 months prior. On physical exam, he was mildly tachycardic with stable blood pressure, and signs of dehydration including dry mucous membranes. Labs prior to this visit confirmed hyperglycemia, hypertriglyceridemia, elevated anion gap, low bicarbonate, and elevated ketones concerning for underlying DKA which finally convinced the patient to present to ED where he met the criteria for hospitalization. Isotretinoin was stopped immediately after admission. In spite of a low c-peptide level (0.8 ng/ml) during hospitalization, immunology testing for type 1 diabetes was negative. However, 4 months later a fasting c-peptide increased to a normal level (3.4 ng/ml). Treatment with basal-bolus insulin in the subsequent months markedly improved his diabetes and he was able to achieve HgbA1c of 5.7%. Conclusion: Rapid worsening of diabetes and presentation with DKA is usually associated with a natural course of type 1 diabetes. In the case of our patient who presented with rapid worsening of diabetes, was asymptomatic while in DKA, had negative type 1 diabetes-related antibodies, and presented with marked hypertriglyceridemia. We suspect isotretinoin to be the culprit in the setting of underlining type 2 diabetes. In contrast to reports of isotretinoin increasing insulin resistance, in our case, there was apparently suppression of insulin release. We would like to bring attention to this case with a proposal for close monitoring of the glycemia and lipid levels in patients with underlying diabetes started on isotretinoin. Presentation: Thursday, June 15, 2023

Five-Year Analysis of Anti-Nuclear Antibody (ANA) and Extractable Nuclear Antigen Antibody (anti-ENA) Immunoblot Test Results

Autoimmune disorders may cause systemic disease in which multiple organs are affected or may also be localized as single-organ involvement. Various ancillary immunological tests used in cases where systemic involvement is observed, and differential diagnosis becomes difficult or non-specific symptoms are observed. For this purpose, investigation of antinuclear antibodies (ANA) and antibodies against extractable nuclear antigens (ENA) in patient serums using various methods is a guide for clinicians. In this study, we aimed to evaluate the effectiveness of ANA and ENA antibody tests by examining the test results, the patients’ demographic data, and the clinics that ordered the tests. In the study, a retrospective review of the results of 37,791 ANA tests studied on serum samples sent to the medical microbiology laboratory of our hospital from various clinics between January 2018 and December 2022 is presented. ANA tests were resulted semi-quantitatively by evaluating the slides prepared using diluted serum samples at a ratio of 1:100 and HEp-2 cells and monkey liver tissue under a fluorescent microscope with the indirect immunofluorescence (IIF) antibody method. Of the patients who requested ANA test, 11,604 (30.7%) were male and 26,187 (69.3%) were female. The mean ages were 43.46 (0-94) and 46.94 (0-96), respectively. Of the samples tested, 18.8% (7,107/37,791) were evaluated as ANA positive. The ANA positivity rate was significantly higher in women (24.8%) than in men (19.7%) (p&lt;0.001). ANA positive samples were re-tested using the anti-ENA immunoblot method. Of the 7,107 ANA-positive patients, 3,809 (53.6%) were found to be anti-ENA positive for at least one specific antibody, while 3,298 (46.4%) were negative. In the anti-ENA profile, antibodies against 11 different antigen types were screened and the most frequently detected antibody was anti-SS-A (22.7%), and this was followed by anti-centromere (12.8%), anti-RNP (10.2%), and anti-dsDNA (9.7%) antibodies. Immunoblot-based anti-ENA tests provide specific information for the diagnosis of autoimmune diseases. In our study, the fact that anti-ENA tests were negative in a significant part of ANA positive patients indicates the inadequacy of the immunoblot test panel and reveals the need for immunoblot tests with wider antibody diversity or any alternative methods.

The association between anti-glutamic acid decarboxylase IgG and hemoglobin A1C among newly diagnosed type 1 diabetes of some Iraqi children in Karbala City

Abstract Background: Type 1 diabetes mellitus (T1DM) is brought on by immune system dysfunction intolerance, invasion of beta cells by autoreactive immunological T cells, degradation of beta cell activity and survival, and extended exogenous insulin treatment. One of the circulation autoantibodies against antigens of pancreatic cell that produce insulin is glutamic acid decarboxylase (GAD IgG antibody) that indicate the stress and/or death of the islet cell in T1D. A blood glucose monitoring test called hemoglobin A1C (HbA1c) is used to determine the average blood sugar level over three months (February, March, and April of 2022). Objective: The purpose of this study is to assess the frequency of anti-GAD IgG and HbA1c in T1DM children, as well as their correlation. Materials and Methods: Seventy individuals with new-onset T1DM (confirmed by clinical signs, including increased urination, intense hunger, intense thirst, and abrupt weight loss, along with a random blood sugar test that is higher than 200 mg/dL and a fasting blood sugar test that is higher than 126 mg/dL) are male and female, ranging in age from 1 to 12 years. Blood was drawn for the biochemical and immunological tests (including HbA1c, fasting blood sugar, C-peptide, anti-islets antibodies, and anti-GAD antibodies). Results: Ninety-four percent of the T1DM patients had positive anti-GAD IgG with a mean concentration of 147 IU/mL, and 6% had negative anti-GAD IgG with a mean value of 9 IU/mL. At the same time, the findings of the current study’s calculation of HbA1c levels revealed that individuals with newly diagnosed T1DM had a total mean average of HbA1c of 10.53. Conclusion: Specifically in T1D that had arisen in extremely young children, autoimmunity was discovered to take part in the glycemic index expressed by glycated hemoglobin average.

Is diabetes a real susceptibility for SARS-CoV-2 oral manifestation?

Furin, a polybasic cleavage enzyme, is increasingly recognized in the pathogenesis of metabolic syndromes like diabetes. Its cleavage action is an essential activation step for the SARS-CoV-2 attachment site at the junction of S1 and S2, the two subunits of the spike. This allows effective cleavage by furin and has a role in determining viral infectivity and host range. The increased expression of the furin enzyme in the saliva is remarkable enough to be noted as a susceptibility factor for diabetic patients. The present study focuses on the qualitative assessment of the furin enzyme through an immunological ELISA test. The study consisted of three groups, each of whom was a COVID-19 recovered patient (n = 20), a diabetic patient (n = 20), and a healthy patient (n = 20). The study assessed significantly increased levels of the furin enzyme generally in diabetic patients and COVID-19 recovered patients as compared to the healthy control group. The estimation of furin in saliva still holds the possibility of being a prognostic marker in many COVID-19 infected patients. Further evidence-based studies are required to establish the same.

Assessment of some immunological and physiological indicators for infected and uninfected coronavirus disease patients

Abstract Background: The most serious respiratory consequences of coronavirus disease (COVID-19) include the common cold, coagulopathy, multiorgan failure, and death. It can also harm essential organs, including the kidney, liver, gastrointestinal tract, lungs, and brain system. Objective: The study’s objectives were to investigate the impact of COVID-19 infection on liver damage by analyzing a range of indicators such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, C-reactive protein (CRP), and d-dimer protein. Materials and Methods: To achieve the study’s goal, blood samples were collected from a group of patients (both males and females), and a series of serological tests were performed, including immunological testing and measurements of CRP, d-dimer, and liver function. Results: In this study of 80 patients (age range between 17 and 70 years), the female-to-male ratio in both groups was 20:20. The difference in CRP level between study groups was statistically significant (P ≤ 0.001). The d-dimer level (ng/mL) in patients with infected COVID was significantly higher (P ≤ 0.001) than in the control group, while there was no statistically significant variation in blood liver enzymes between infected and noninfected COVID groups. According to statistical analysis, there is no discernible gender difference between groups of noninfected people and infected patients. Conclusion: The study findings indicate that there are no significant differences between infected males and females when compared to the comparison group; however, there are distinct variances in CRP and d-dimer levels in the infected group. The results of liver function tests and enzyme measurements revealed no significant changes between the infected and healthy groups.