The Role of Vitamin D on Thyroid Antibodies in Patients with Chronic Autoimmune Thyroiditis

Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-inflammatory and immunomodulatory properties.Chronic autoimmune thyroiditis is a disease of autoimmune genesis,in which lymphocytic infiltration gradually destroys thyroid tissue.There are some evidences about vitamin D deficiency and the development of chronic autoimmune thyroiditis.The article has reviewed the current literature about the impact and the benefits of vitamin D on thyroid antibodies levels.

Selenium Supplementation Alleviates Autoimmune Thyroiditis by Regulating Expression of Th1/Th2 Cytokines

Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.

Interferon-induced progression of autoimmune thyroiditis with enlarged thyroid glands in gynecological patient: A case report and literature review

A case report presents a progression of autoimmune thyroiditis with an abnormal enlargement of the thyroid glands and increased thyreotropin hormone concentration-associated with interferon treatment in human papillomavirus infected patient with the autoimmune thyroiditis and a daily L-thyroxin hormone replacement therapy background. Observation was supplemented with a brief review of literature and discussion. On the basis of this observation and a brief review of literature authors suggested that the potential adverse effects of interferon therapy are overbalanced than its benefits for gynecological patients, therefore any interferon treatment should be recommended with strict indications as well as after screening of conditions and functions of thyroid glands and other interferon target organs to avoid interferon treatment side effects. Practitioners especially gynecologists should inform their patients about pleiotropic interferon effects and its high frequent and wide range side effects before to start such kind of treatment.

Intervention and immune regulation of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis model rats

Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 were randomly selected as the blank group,and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model.After the model was established,they were randomly divided into three groups:the model group,the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group,which were continuously gavaged for 2 months.The anti thyroid autoantibodies,thyroid function,IL-38 and Th17/Treg distribution were measured.The pathological changes of thyroid tissue were observed by HE staining.Results:Compared with the blank group,the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05).Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed,the shape was irregular,and the colloid distribution was uneven,indicating that the modeling was successful.Compared with the model group,the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05).And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group(P<0.05).Compared with the blank group,the levels of T3,T4,FT3 and FT4 in the model group increased,the level of IL-38 decreased,the proportion of Th17 increased,and the ratio of Th17/Treg increased(P<0.05).Compared with the model group,T4 level decreased,IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group(P>0.05).There was no significant difference in Treg ratio among the groups.Conclusion:Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats,and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.

Immune Intervention Effects on the Induction of Experimental Autoimmune Thyroiditis

To explore im mune intervention effects of the combined use of cycloporin A (Cs A ) and 1,2 5 - dihydroxyvitam in D3[1,2 5 (OH ) 2 D3]at low doses on experimental autoim mune thyroiditis (EAT) ,porcine thyroglobulin (p TG) was injected into a CBA mouse at the dose of 10 0μg on day 0 and day14 to establish the model of EAT.The immune prevention group from day0 to day2 8, and treatm ent group from day10 to day38were daily adm inistered Cs A(10 mg/ kg) intragastri- cally and/ or1,2 5 (OH) 2 D3(0 .2 μg/ kg) ip.After im munized by p TG,the m ice were sacrificed on day2 8and day38to examine their thyroid gland pathologically,and to check the levels of serum porcine thyroglobulin antibodies (p TGAb) ,porcine thyromicrosom al antibodies (p TMAb) .The incidences of EAT in the immune prevention group and treatment group,with administration of low dose of Cs A and 1,2 5 (OH) 2 D3,were decreased respectively by 4 4 .4 4 % and 37.5 0 % .Those of severe disease in the two groups were decreased respectively by71.4 3% and6 0 .32 % .The levels of serum p TGAb and p TMAb in the imm une prevention group were lower than those of the positive control group.It was concluded thatcombined use of Cs A and1,2 5 (OH) 2 D3at low doses could effectively prevent EAT with a synergic effect.

Autoimmune thyroiditis presenting as psychosis

桥本氏甲状腺炎系一种罕见的自身免疫性疾病,血液中含有大量的自体抗体,主要表现为神经系统症状。有文献报道桥本氏甲状腺炎会出现一些行为症状,而没有明显的神经症状。我们报告的病例较少见,与其他的桥本氏甲状腺炎的常见临床表现不同。

Prevalence of coeliac disease in patients with autoimmune thyroiditis in a Turkish population

AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay.Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS:Eight patients(5.9%)and one control subject(0.8%)were positive for IgA tissue transglutaminase antibody(OR:7.38,95% CI:0.91-59.85,P = 0.04).Six patients and one control agreed to take biopsies.Histopathological examination revealed changes classified as Marsh Ⅲa in one,Marsh Ⅱ in one,Marsh Ⅰ in two,and Marsh 0 in two patients with autoimmune throiditis,and MarshⅠin one blood donor.CONCLUSION:Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients.Our findings need to be confirmed in a larger series of patients.

Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule(补中益气颗粒)on experimental autoimmune thyroiditis in female rats

OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

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.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune disease.AE was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May 2018.Currently,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

The anti-inflammatory effects of exercise on autoimmune diseases:A 20-year systematic review

Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Management of autoimmune hepatitis induced by hepatitis delta virus

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.