GAD65 Research Articles

The clinical relevance of anti-glutamic acid decarboxylase antibodies in children with encephalitis/encephalopathy.

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy.

Associations between glutamic acid decarboxylase antibodies, oxidative stress markers, and cognitive capacity in adolescents who stutter

In this study, we amid to evaluate the correlation between the change in the expressed levels of anti-GAD antibodies titers, oxidative stress markers, cytokines markers, and cognitive capacity in adolescents with mild stuttering. Eighty participants (60 male/20 female) with the age range of 10–18 years with moderate stutteringparticipated in this study. To assess the stuttering and cognitive function, stutteringseverity instrument (SSI-4; 4th edit.)and the LOTCA-7 scores assessment were applied respectively in all subjects. In addition, serum GAD antibodies, cytokines like TNF-α, CRP,and IL-6 withtotal antioxidant capacity and nitric oxide as oxidative stress markers were estimated using calorimetry and immunoassay techniques.The results showed that good cognitive capacity was reported in about 56.25 % of the study population (n = 45) with a 117.52 ± 6.3 mean LOTCA-7 score. However, abnormal cognitive function was identified in 43.75 % of the study population (n = 35); they were categorized into moderate (score 62–92, n = 35), and poor (score 31–62; n = 10). There were significant associations between cognitive capacity reported and all biomarkers. The expression of GAD antibodies is significantly associated with the degree of cognitive capacity among students with stuttering. Significant association with the reduction (P = 0.01) in LOTCA-7 score domains, particularly orientation, thinking operations, attention, and concentration among students with variable cognitive capacity compared to controls. In addition, the expressed higher GAD antibodies in students with moderate and poor cognitive capacity showed to be significantly correlated with both elevated concentrations of cytokines; TNF-α, CRP, and IL-6, and the reduction of TAC and nitric oxide (NO) respectively. This study concludes that abnormality of cognitive capacity showed to be associated with higher expression of GAD antibodies, cytokines, and oxidative stress in school students with moderate stuttering.

Use of insulin degludec/aspart after resolution of euglycemic diabetic ketoacidosis associated with dapagliflozin in a female patient with newly diagnosed maturity onset diabetes of the young type 3

Abstract Introduction Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by beta cell dysfunction. MODY presents generally at a young onset, and usually does not prone to ketosis. MODY should be distinguished from type 1(T1D) or type 2 diabetes(T2D), because the treatment modalities may be different. In this case, we aimed to emphasize the successful use of insulin degludec/aspart (IDegAsp) after resolution euglycemic diabetic ketoacidosis (euDKA) in a patient latterly diagnosed with MODY. Clinical Case A 39-year-old female patient was referred to our clinic with severe hyperglycemia. SMBG results revealed that blood glucose levels were about 300–400 mg/dL indicating severe hyperglycemia. She has been followed up for T2D 15 years and had been taking oral antidiabetic regimen until 6 months ago. Insulin glargine was prescribed 6 months ago, but she gave up insulin and had been taking linagliptin 5 mg/day and dapagliflozin 10 mg/day. The previous history was remarkable for arrhythmia which was treated with ablation 15 years ago. Maternal history of T2D was present. On physical examination, heart rate was 100/min, and systemic examination findings were in normal range except for central obesity. Laboratory evaluation revealed that fasting blood glucose was 212 mg/dL, HbA1c 10.2%, creatinine 1.1 mg/dL, and ketone 3+ in urinalysis. Arterial blood gas analysis revealed mild acidosis (pH 7.25, HCO3 18 mmol/L). The patient was hospitalized with a diagnosis of euDKA. Intravenous hydration with 0.9% NaCL and regular insulin was administered, and oral antidiabetic medications were stopped. In the follow-up, intensive insulin regimen (preprandial insulin glulisine 3×5 unit and basal insulin glargine 1×15 unit) was given after the resolution of euDKA. Although dose adjustments, two attacks of near-hypoglycemia (71 and 77 mg/dL) were detected in the first week after resolution of euDKA. IDegAsp (premeal 2×12 unit) was substituted for glargine and glulisine. Due to the maintenance of glycemic regulation by oral antidiabetic regimen for a long period, and the existence of maternal history of T2D, genetic analysis was performed with a pre-diagnosis of MODY. To exclude T1D, we demonstrated that autoantibodies (islet cell antibody 5.01 U/mL, and Anti-GAD antibody 7.74 IU/mL) for T1D were negative. HNF1A heterozygous mutation was detected, and MODY type 3 was diagnosed. HbA1c level was gradually regressed to 8.8%, and then to 6.3%. By the diagnosis of MODY type 3, gliclazide treatment was considered. Basal fasting C-peptide level was measured as 1.22 ng/mL. The antidiabetic regimen was revised as linagliptin 5 mg/day and gliclazide 30 mg/day, and insulin was stopped. Conclusion Some types of MODY is associated with mild hyperglycemia, however some others necessitate insulin treatment. The number of reports regarding the use of IDegAsp in MODY is limited. We reached HbA1c target with IDegAsp in a patient with MODY type 3 after resolution of euDKA.

Prolonged remission in latent autoimmune diabetes of adults (LADA): Is insulin resistance a major influence?

Abstract Introduction Type 1 diabetes mellitus (T1DM) is a chronic inflammatory disease that courses with high serum glucose levels as a result of pancreatic beta cell destruction and subsequent insulinopenia. LADA is a type of autoimmune diabetes where damage to the beta cell occurs much slower. The natural history of type 1 diabetes is very heterogeneous and variable. This is especially true for LADA with several possible different clinical courses due to a wider variety of pancreatic cell destruction and insulin resistance. Clinically overt diabetes ensues when more than 80% of pancreatic cell mass is loss. After treatment initiation partial disease remission is common, especially in children. However complete remission is rare, and remission lasting for over a year is even rarer, with few reports published in literature. Some agents such as vitamin D and DPP4 inhibitors have been presented has having potential immunomodulatory effects. Clinical Case A 36-year-old man with grade 1 obesity (BMI 33 kg/m2) presented at the emergency department with symptoms of insulinopenia (polyuria and polydipsia in the previous 3 months) and hyperglycemia (capillary blood glucose >500mg/dL). Ketonemia was negative and pH was normal on blood gas analysis The diagnosis of diabetes mellitus was made and insulin therapy was instituted on a basal-bolus regimen. At the first follow-up appointment, due to his morphotype and familiar history of type 2 diabetes (mother diagnosed at 52 years of age), he stopped short-acting insulin and was started on metformin and SGLT2 inhibitor. A week later he was admitted in the hospital in euglycemic ketoacidosis. Initial workup revealed positive anti-GAD 41.8 U/mL, HbA1C 9.8%, C-peptide 1.83 ng/mL, serum insuline 17.4 uU/mL. Consequently, metformin and SGLT2 inhibitor therapy was stopped, and the patient resumed basal bolus insulin regimen. He then remained under a basal insulin without need of meal-time insulin bolus, progressively lowering the basal insulin dose until suspension four months later. Simultaneously, lifestyle changes were implemented with significant weigh loss (BMI 33 > 26.4 kg/m2 at the time of insulin suspension). After 3 years of follow-up the patient remains without need of antidiabetic therapy, with normal Hba1c 5.3%. Anti-GAD antibodies remain positive (39.4 U/mL) but C-peptide and serum insulin are within the reference range (1.69 ng/mL [1.1–4–4], 6.9uU/mL [2.6–25], respectively). Conclusion Prolonged disease remission in type 1 diabetes is rare. This case highlights an especially long “honeymoon” period in a patient with LADA. Obesity and insulin resistance probably played a role in the initial patient presentation, and its improvement probably helps to justify this prolonged remission. In spite of the family history of diabetes, other types of diabetes seem unlikely due to positive antibodies and SGLT2 inhibitor associated euglycemic ketoacidosis.

Update information on type 1 diabetes in children/adolescents and adults.

Update information on type 1 diabetes in children/adolescents and adults.

Correlation analysis between cytokines' profile, autoimmune antibodies and the duration of type 1 diabetes: A case control study in a specialized children's centre in Riyadh.

The aim of this study was to investigate the role of cytokines in children with T1D living in Saudi Arabia and their correlation with disease duration and autoimmune antibody markers. A case-control study was conducted in the endocrine clinic of King Abdullah Specialized Children's Hospital in Riyadh. A total of 274 T1D and healthy control children were enrolled in the study. 5mL of venous blood samples were collected in the morning after 9 to 12h of fasting in BD Vacutainer® EDTA tubes and centrifuged at 250g for 15min at. Plasma was then stored at -20°C for detection of anti-islet, anti-GAD antibodies (Abs), and C-peptide using commercial ELISA kits from Thermo Fisher Scientific. The levels of cytokines were measured using commercial sandwich ELISA kits from Abcam. Median differences in cytokine levels (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, IL-18, IL-21, IL-35, and IL-37) were significantly higher in T1D patients compared with healthy controls (p-value < .001). Spearman's Rho correlation indicated that TNFα, IL-1β, IL-4, IL-10, IL-13, and IL-21 correlated significantly with T1D Abs (p-value = .01). HbA1C correlated negatively with IL-35 and IL-37, and positively with IL-18 (p-value = .01). Linear regression analysis showed a significant increase in anti-glutamic acid antibodies (GAD) in patients with >3years of T1D duration. Autoantibodies remained positive at high levels in our patients over a 3-year duration of the disease and correlated with specific cytokines. The clear correlations with disease duration and profile of specific cytokines could be targets for future therapeutic interventions.

Stiff Person with Anti-GAD Antibodies

Stiff Person with Anti-GAD Antibodies

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases. The aim of the study was to evaluate the population of NK cells and pancreatic β cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases. The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software. The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings. The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

New-Onset Idiopathic Generalised Seizure in a Nigerian Teenager with Type 1 Diabetes Mellitus

We described a case of a 19-year-old female with a new onset Idiopathic Generalised seizure and Type 1 Diabetes mellitus(TIDM). Diagnosis of epilepsy is based on at least two unprovoked seizures. Anti-glutamic acid decarboxylase (Anti-GAD) antibodies positivity is a potential link between TIDM and epilepsy as seen in this case similar to other report. There is a need for careful glycaemic control in children with epilepsy and TIDM as hypoglycemia-induced seizure must be avoided using appropriate insulin dosage.

Prevalência de outras doenças autoimunes em crianças e adolescentes com diabetes mellitus tipo 1

OBJECTIVE: To evaluate the prevalence of autoimmune markers associated with beta-pancreatic cells, autoimmune thyroid diseases and celiac disease through research of anti-glutamic acid decarboxylase antibodies (GADA), antiislet cell antibodies (ICA), anti-insulin antibodies (IAA), anti-tyrosine phosphatase (IA-2A), anti-transglutaminase antibodies (anti-tTG), anti-endomysium anti-transglutaminase antibodies (EMA ), immunoglobulin A (IgA), thyroperoxidase antibodies (anti-TPO) and thyroglobulin antibodies (anti-TG), in addition to related hormonal measurements in children and adolescents with type 1 diabetes mellitus. METHODS: Observational, longitudinal study, with retrospective data collection by reviewing the medical records of 92 children and adolescents, diagnosed with DM1 between January 2014 and December 2016, seen at a Pediatric Endocrinology service of a tertiary hospital in Curitiba- PR. RESULTS: At the diagnosis of DM1, the prevalence of anti-GAD antibody positivity was 69.6% (n = 79), ICA 42.9% (n = 70), IAA 32.8% (n = 64), IA2 of 60.6% (n = 33). Positivity for markers of other associated autoimmune diseases was 27.4%, EMA 6.0% (n = 50), anti t-TG IgA 12.5% (n = 8), anti-TPO 13, 1% (n = 84) and 22.9% anti-TG (n = 83). Autoimmune thyroid diseases were the most frequently found comorbidity at diagnosis (22.1%). Among patients with positivity for antithyroid antibodies, 19% developed clinical hypothyroidism. CONCLUSIONS: Patients with DM1 have a high prevalence of autoimmunity. The importance of screening for such diseases to diagnosis and clinical follow-up is reinforced, in order to assist in predicting the development of associated diseases and their complications, as well as providing adequate treatment.

Therapeutic plasma exchange in the management of stiff person syndrome spectrum disorders: a case series and review of the literature.

Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often requires immune therapies, especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD remains uncertain. To describe the safety, tolerability, and efficacy of TPE in patients with SPSD. A retrospective observational study. A retrospective review of SPSD patients seen at Johns Hopkins Hospital (JHH) from 1997 to 2021 was performed. Patient demographics/history, examination/diagnostic findings, treatment response, and TPE-related complications were recorded. Assessment for any associations between clinical characteristics, including age, sex, clinical phenotype, and time on immunotherapy, and response to TPE 3 months after treatment was performed. A subgroup of 18 patients treated with TPE at JHH and 6 patients treated with TPE at outside institutions were evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment. Literature review of SPSD and TPE was also conducted. Thirty-nine SPSD patients were treated with TPE (21 at JHH and 18 at outside institutions); median age 48 years, 77% female, median modified Rankin Scale 3; mean initial anti-GAD65 antibody titer was 23,508 U/mL. Twenty-four patients (62%) had classic SPS, 10 (26%) had SPS-plus, 2 (5%) had progressive encephalomyelitis with rigidity and myoclonus, and 3 (8%) had pure cerebellar ataxia. All patients were on symptomatic treatments, 30 (77%) previously received IVIg, and 3 (8%) previously received rituximab. Four patients (10%) had a TPE-related adverse event. One developed asymptomatic hypotension, another had both line thrombosis and infection, and two had non-life-threatening bleeding events. Twenty-three (59%) patients reported improvement in symptoms after TPE. Of the subgroup of 24 patients evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment, 14 (58%) required fewer GABAergic symptomatic medications. Literature review identified 57 additional patients with SPSD; 43 (75%) reported temporary improvement after TPE. The majority of patients treated with TPE had improvement. Moreover, most patients evaluated for any change in usage of symptomatic medications after the TPE treatment no longer required as much symptomatic medications months after TPE. TPE appears safe and well-tolerated in SPSD. Further studies are needed to assess the long-term efficacy of TPE in SPSD and identify which patients may benefit the most from TPE.

Psychiatric presentation and somatic complications in anti-glutamic acid decarboxylase (GAD) antibodies: A case report

Autoimmune encephalitis represents a rapidly evolving group of immune-mediated disorders characterized by brain inflammation and neuropsychiatric symptoms, resulting from antibodies targeting neuronal cell surface proteins, ion channels, or receptors. Among the antigens involved, autoantibodies against NMDAR, AMPAR, GAD, GABA-AR/BR, LGI1, CASPR2, mGluR5, DPPX, and Neurexin-3a are significant in the pathogenesis of autoimmune encephalitis (AE) in adults. Glutamic acid decarboxylase (GAD), specifically its isoform GAD65, is a key enzyme in the production of GABA, and its antibodies are associated with conditions like temporal lobe epilepsy and various neurological syndromes including stiff-person syndrome (SPS), limbic encephalitis, and cerebellar ataxia. Psychiatric symptoms, such as behavioral changes, memory loss, and executive function impairment, are common in anti-GAD antibody-associated encephalitis. We present the case of D.B.-V., a 40-year-old male with no psychiatric history, who developed severe neuropsychiatric symptoms leading to a diagnosis of anti-GAD autoimmune encephalitis. Initial symptoms included headache, fever, and rapid progression to severe confusion and altered consciousness, requiring intubation. MRI findings and anti-GAD antibodies in the cerebrospinal fluid confirmed the diagnosis. Despite immunotherapy with IVIG, plasmapheresis, and Rituximab, the patient remained agitated and noncompliant, necessitating psychiatric intervention. The management was complicated by infections and fluctuating metabolic parameters, highlighting the need for a multidisciplinary approach. After significant medical and psychiatric treatment, the patient was transferred to a specialized nursing home, with persistent cognitive and functional impairments. This case underscores the importance of early recognition and a comprehensive, multidisciplinary approach to managing autoimmune encephalitis, addressing both neurological and psychiatric symptoms to improve long-term outcomes.

Co-Occurring NMDA-Receptor and Anti-GAD65 Antibodies in the CSF of a Patient With Encephalitis: Case Report

Objective We describe a 58-year-old woman who presented with rapid cognitive changes and was found to have concurrent CSF NMDA and GAD65 receptor antibodies. Background Antibodies against NMDA and GAD65 receptors are associated with highly morbid autoimmune encephalitides. One case of co-occurring NMDA-R and anti-GAD65 antibodies in a patient with progressive cognitive changes and type I diabetes has previously been described. Herein, we describe a case of a previously high-functioning woman who experienced rapidly progressive cognitive changes secondary to autoimmune encephalitis (AE) with co-existent NMDAR and GAD65 antibodies. Design/Methods NA. Results A 58-year-old woman with adult-onset insulin-dependent diabetes mellitus, hypertension, and prior left-sided Bell's palsy presented to medical care for subacute cognitive decline characterized initially by inattention and difficulty with activities of daily living, progressing to profound global aphasia and seizures. Diagnostic testing revealed GAD65 antibody positivity in serum (33 nmol/L) and CSF (17.3 nmol/L) and negative serum but positive CSF NMDAR antibody. CSF showed pleocytosis (37 nucleated cells, 97% lymphocytes), elevated glucose (109 mg/dL), and normal protein (41 mg/dL). EEG showed right temporal epileptiform discharges. MRI was unrevealing. She was treated with IV steroids, IVIg, and rituximab, and has slowly improved on follow-up. Conclusions Co-existent CSF anti-NMDAR and anti-GAD65 AE is not well-described in the literature. While this patient's serum GAD65 titer was in a range that correlates with neurologic autoimmunity, it was not as high as is typically reported in AE, and could simply be a marker of her insulin-dependent diabetes. However, it was also definitively positive from the CSF, which usually correlates well with GAD65-associated AE. Clinically, the patient had AE features that can be seen associated with either NMDAR and/or GAD65 antibodies. It is interesting to consider whether the GAD65 positivity is most likely to correlate with the patient's adult-onset diabetes, her AE, or both.

Acute Autoimmune Encephalitis With Features of Bickerstaff Brainstem Encephalitis (BBE) and Two Abnormal Autoantibodies Presenting With Prominent Cerebellar Abnormality on MRI–A Case Report

Objective To present an unusual cerebellar imaging finding of a patient with clinical features of BBE Background BBE is characterized by progressive ataxia, ophthalmoplegia and impaired consciousness. Magnetic resonance imaging (MRI) of the brain is usually normal. However, rare T2 Flair changes have been reported. Scarcity of cerebellar findings on imaging led to the controversy of peripheral vs central etiology for the ataxia. Despite other modalities including positron emission tomography, magnetic resonance spectroscopy and molecular level evidence pointing towards involvement of the cerebellum, MRI is usually unrevealing. Design/Methods A 62-year-old woman presented with acute onset ataxia with multiple falls, dysarthria, diplopia, and blurred vision that started 3 days prior to presentation. She had left face angioedema couple days after her flu inoculation 6 weeks prior to presentation. Her exam revealed normal mental status, scanning speech, bilateral dysmetria and ataxia as well as left-sided facial palsy, square wave jerks and hyperreflexia. CSF showed 30 RBC, 17 WBC, normal glucose, and elevated protein of 68 mg/dl. No infectious etiologies were identified. MRI brain showed infratentorial leptomeningeal enhancement with T2 hyperintensities in the both cerebellar hemispheres. Anti-GQ1b antibodies were 51 IV (negative &lt; 30 IV) and anti-GAD65 antibodies were also weakly positive only in serum, 0.12 nmol/L (negative &lt; 0.02 nmol/L). Results She was diagnosed with autoimmune encephalitis and treated with IV methylprednisolone and IVIG. She rapidly improved clinically, and her imaging findings resolved. Conclusions We demonstrated prominent cerebellar imaging findings and good recovery in a patient with anti-GQ1b and mild anti-GAD65 seropositive autoimmune encephalitis. Our case is the first reported double positive autoimmune encephalitis with features of BBE and direct cerebellar involvement

Characterization of Retinal Nerve Fiber Layer Thickness in a Cohort with Glutamic Acid Decarboxylase 65 and Glycine Receptor Autoimmunity

Objective To describe the retinal nerve fiber layer (RNFL) with the demographic and clinical profile in patients with glutamic acid decarboxylase 65 (GAD65) and glycine receptor (GlyR) neurological autoimmunity. Background GAD65 and GlyR autoimmunity can cause a wide range of clinical phenomena, including stiff-person spectrum disorder (SPSD) and epilepsy. Both GAD65, through γ-aminobutyric acid-ergic neurons, and GlyR interact in the retina. Optical coherence tomography (OCT) has previously been used in a variety of neurological disorders to establish baseline characteristics and monitor disease course. This presents a noninvasive opportunity to evaluate for a biomarker that may assist with the treatment of these rare but debilitating disorders. Design/Methods OCT measures of RNFL by sectors were studied in patients with GAD65 and GlyR neurological autoimmunity and compared to that of 148 healthy control eyes. Patients' baseline characteristics were also reviewed retrospectively from medical records. Results Of the 14 patients included in this study, 12 patients were female, and the mean age was 52.6 ± 16.8 (22-79) years when OCT was performed. Ten had GAD65 autoimmunity and 4 had GlyR autoimmunity. Patients with GAD or GlyR autoimmunity showed lower RNFL thickness in multiple sectors compared to the healthy control group. This result was most apparent in the anti-GAD65 antibody subgroup. Eleven patients had SPSD, one patient had epilepsy, and two had non-specific symptoms. Conclusions This study provides insight into baseline RNFL thickness in a group with GAD65 and GlyR autoimmunity, two conditions that may produce varied symptoms. While limited by sample size, RNFL thinning was seen in the GAD65 and GlyR autoimmunity groups, and it was most evident in the anti-GAD65 subgroup. This provides a baseline characterization and suggests that future studies should be conducted to determine the utility of OCT as a biomarker for these conditions.

Therapeutic Plasma Exchange in the Management of Stiff Person Syndrome Spectrum Disorders: A Case Series and Review of the Literature

Objective To describe the safety, tolerability, and response to TPE in patients with SPSD. Background Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often require immune therapies especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD is unclear. Design/Methods A retrospective review of medical records for patients with SPSD seen at Johns Hopkins Hospital was performed. Patient characteristics, exam findings, diagnostic studies, treatment response and TPE-related complications were recorded. We also conducted linear regression models to assess for possible predictive factors for TPE response. Literature review of SPSD and TPE was also conducted. Results Thirty-six SPSD patients were treated with TPE; mean age was 48 years, 81% female, and average anti-GAD65 antibody titer was 42352 U/mL (range, 0-309,902). Twenty-two patients had classic SPS, 10 had SPS-plus, and 3 had other phenotypes. Thirty-three patients were treated for acute exacerbations, and 3 were on maintenance TPE. There were 4 (11.1%) TPE-related complications (catheter infection, catheter thrombosis, hemorrhage), but no deaths or anaphylaxis. Twenty patients (55.6%) reported improvement in symptoms after TPE, 13 reported no change, and 3 reported worsening of symptoms. Of the 36 total patients who received TPE, 21 received TPE at Johns Hopkins Hospital for an acute exacerbation of their condition, with 12 requiring fewer anti-spasmodic medications 3 months after TPE treatment. There were no predictive factors in a positive treatment response to TPE. Literature review identified 42 more patients; 69% of these patients reported a temporary improvement in their condition. Conclusions We describe the safety and tolerability of TPE in patients with SPSD and show that TPE-related complications are uncommon and manageable. Additionally, many patients with SPSD derived improvement with TPE. Further studies could help inform clinicians when to use TPE in SPSD.

PSUN250 Empagliflozin Induced Bladder Cancer in an Adult Patient With Latent Autoimmune Diabetes

Abstract Sodium glucose cotransporter type 2 (SGLT2) inhibitor is a novel class of antidiabetic agent. The association of SGLT2 inhibitors and incidence of bladder cancer has not been well established due to few numbers of cases and not enough length of exposure. Here we describe a case of bladder cancer developed one year after empagliflozin exposure in a patient with latent autoimmune diabetes. Case description A 51-year-old man presented to our endocrine clinic with a one-year diagnosis of type 2 diabetes mellitus. His glycosylated hemoglobin (HbA1c) was 8% on maximum dose metformin and well adherence to diet. The patient had no significant past medical history and his body mass index was 23.6 kg/m2. Empagliflozin 25 mg daily was added to his regimen, in addition to sulfonylurea and dipeptidyl peptidase-4 (DPP-4) inhibitor drugs. The patient continued to have persistent hyperglycemia despite medical therapy with HbA1c ranged between 7.5-7.9%. After one year, he presented with fatigue, unintentional 7-kg weight loss and perianal pain. A transrectal ultrasound of the pelvis showed a 10-mm solid lesion in the urinary bladder. He underwent transurethral resection of bladder tumor; pathology showed a low grade papillary urothelial carcinoma with focal areas of high grade. Empagliflozin was discontinued and due to persistent hyperglycemia, further labs were requested. Fasting blood glucose of 265 mg/dl, HA1c of 7.9%, anti-GAD antibody was positive 37.52 u/ml (&amp;lt;10.0), C-peptide of 0.51 ng/ml (0.37-1.47), insulin of 2.0 mu/ml (2.6-24.9). These findings suggested latent autoimmune diabetes with mild pancreatic reserve. Patient was then started on insulin therapy of Glargine and Aspart. Conclusion The use of SGLT2 inhibitors in patients with autoimmune diabetes may have a higher risk of bladder cancer as compared to patients with type 2 diabetes. An individualized selection of antidiabetic agent with consideration of proper diagnosis is recommended to prevent a serious consequence. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

IMMUNE CHECKPOINT INHIBITOR-INDUCED DIABETIC KETOACIDOSIS: A RARE SIDE EFFECT

IMMUNE CHECKPOINT INHIBITOR-INDUCED DIABETIC KETOACIDOSIS: A RARE SIDE EFFECT

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and 1H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.

Stem cell therapy for type1 diabetes with transplantation of stem cells into the Omental pouch, peritoneum, and blood, experimental study

IntroductionType 1 diabetes is a dreadful autoimmune disease of childhood with incidence of 0.26/1000 children in India. To develop a new, cheap, and effective treatment for this disease, we invented an autologous Stem cell therapy for type 1 diabetes in which stem cells are transplanted into the Omental pouch, peritoneum, and blood. The Omental pouch stem cell operation in the therapy is reported for the first time in the medical literature. Materials and methodsLast 5 years I treated 21 patients of Type 1 diabetes with autologous stem cell therapy and in the same period, a group of 26 patients of Type 1 diabetes with conventional treatment of Insulin injections was put as a control group. Blood sugar fasting and post prandial, Anti Gad antibody titer, Glycosylated Hb and C peptide levels and weight of patient and total Insulin requirement in 24 h were the variables to be measured before the therapy and after the therapy. Stem cells were harvested from patients own bone marrow and separated by density gradient method. An infusion of 20 mg/kg methylprednisolone in 100 ML normal saline given intravenously over 1 h prior to the therapy. The total average numbers of cells harvested were 7.86 × 107. One third quantity of isolated stem cells were put into the Omental pouch through no. 7 IFT, another one third into peritoneal cavity through no. 10 IFT and remaining third is given IV in 100 ml normal saline. ResultsThe minimum follow up was 6 months and maximum of 4 years. In the therapy group, the average weight gain after one year of therapy, daily requirement of Insulin and its drop after therapy, drop in HbA1c levels, drop in fasting and post prandial blood sugar, rise of C peptide levels and drop in Anti-GAD antibody titer were measured and was found to be statistically highly significant. The same parameters were measured in control group and was not statistically significant. There were a few side effects noted after stem cell therapy such as mild skin rash, nausea, and pain in abdomen. DiscussionIn autologous bone marrow derived stem cell therapy, cells are transplanted into the Omental pouch, peritoneum, and blood. Cells transplanted in the Omental pouch get vascularized like a split skin graft. Omental surface has far less cellular immunity than blood, hence, if some of these cells get converted into Islets like cells producing Insulin, then they are less vulnerable to damage by the immune system. It means that the Omental pouch may act as a new biological pancreas producing Insulin. Stem cells injected intravenously reach the pancreases and may get differentiate into Islet like cells due to specific growth factors released by pancreas. Stem cells can reverse autoimmunity by their immunomodulatory function. Stem cells transplanted in peritoneum grow longer due to large surface area and little cellular immunity and secrete growth factors and cytokines for a long time which can rejuvenate existing Islets of Langerhans. The therapy group had substantially good results compared to the control group and the difference was statistically highly significant. ConclusionsAutologous stem cell therapy was safe, and effective for the long term for the treatment of Type 1 diabetes. We need a greater number of cases and a longer follow up to make it better. The therapy creates a lot of hope for Type 1 diabetes patients as it can be easily repeated any number of times.