Classical Autoimmune Diseases Research Articles

Problems of prescribing immunosupressive therapy to a rheumatological patient with chronic viral infection. Clinical case presentation

In rheumatological practice, overlap syndrome (“overlap-syndrome”) is often encountered, which is manifested by the presence of diagnostic signs of more than one of the six classic systemic autoimmune diseases. The presence of chronic viral infections significantly complicates drug therapy. The article presents the history of the disease of a 46-year-old patient who was diagnosed with an overlap syndrome in the form of a combination of idiopathic polymyositis with antisynthetase syndrome and rheumatoid arthritis. The complexity of treating the patient was determined by the identification of active chronic viral hepatitis C. A multidisciplinary approach to the management of the patient in compliance with the principles of rational pharmacotherapy is described.

New and future perspectives in familial Mediterranean fever and other autoinflammatory diseases.

Systemic autoinflammatory diseases are a group of disorders characterized by sterile episodes of inflammation resulting from defects in the innate immune system. In contrast to classical autoimmune diseases, where circulating autoantibodies and the adaptive immune system are involved, these conditions involve excessive presence of proinflammatory cytokines leading to inflammatory attacks. Excessive cytokine production, functional mutations in regulatory pathways, excessive interferon production, defects in the nuclear factor-kappa B signaling pathway, abnorARCHmal protein folding, and complement activation are the mechanisms leading to autoinflammatory diseases. A defect in the mTOR pathway and trained immunity are newly discovered possible causes in pathogenesis. Early onset and severe forms of classical rheumatological diseases have been more frequently associated with autoinflammatory diseases in the last decade. Therefore, monogenic autoinflammatory diseases should be considered in rheumatic diseases with family history, consanguinity, early onset, and severe disease. The combination of functional and genotyping research will help to identify unclassified patients. The optimal treatment strategy remains uncertain, functional studies such as interferon signature and cytokine profiling, may prove valuable in guiding the treatment process. Stem cell transplantation strategies in autoinflammatory diseases with partial response to biological therapies can be considered. Autoinflammatory diseases are becoming increasingly complex and are bringing new perspectives to already known rheumatic diseases. Although we have effective treatments, we are still far from personalized recommendations.

CMPK2 Promotes CD4+ T Cell Activation and Apoptosis through Modulation of Mitochondrial Dysfunction in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by abnormal autoantibodies, immune complex deposition, and tissue inflammation. Despite extensive research, the exact etiology and progression of SLE remain elusive. Cytidine/uridine monophosphate kinase 2 (CMPK2), a mitochondrial nucleoside monophosphate kinase, has garnered attention for its potential involvement in the development of various diseases, including SLE, where it has been observed to be dysregulated in affected individuals. However, the specific involvement of CMPK2 in the pathogenesis of SLE remains unclear. This study aims to clarify the expression level of CMPK2 in SLE CD4+ T cells and explore its impact on CD4+ T cells. The expression levels of the CMPK2 gene and the corresponding CMPK2 protein in CD4+ T cells of SLE patients were quantified using RT-qPCR and Western blot, respectively. Immunofluorescence and RT-qPCR were used to assess the mitochondrial function of SLE CD4+ T cells. Flow cytometry was used to assess CD4+ T cell activation and apoptosis levels. The impact of CMPK2 on CD4+ T cells was investigated by gene transfection experiment. We found that CMPK2 was significantly upregulated in SLE CD4+ T cells at both gene and protein levels. These cells demonstrated aberrant mitochondrial function, as evidenced by elevated mitochondrial reactive oxygen species (mtROS) levels, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) copy number. Flow cytometry revealed a notable increase in both apoptosis and activation levels of CD4+ T cells in SLE patients. Gene transfection experiments showed that suppressing CMPK2 led to a significant improvement in these conditions. These findings suggest that CMPK2 may be involved in the pathogenesis of SLE by regulating mitochondrial dysfunction in CD4+ T cells and thus affecting CD4+ T cell activation and apoptosis. Our study may provide a new target for the treatment of SLE.

Germline variation and risk of immune-related adverse events (irAEs): A real-world BioVU study.

10582 Background: IrAEs are prevalent in patients treated with immune checkpoint inhibitors (ICI) and mimic classical autoimmune diseases. IrAE risk prediction could improve clinical decision making and patient safety for ICI-treated patients. Classical autoimmune diseases show strong associations with germline polymorphisms and with Human Leukocyte Antigen (HLA) variants, though it is unclear if these same genetic risk factors predispose to irAEs. To identify both tolerant and irAE patients, we mined Vanderbilt University Medical Center (VUMC) BioVU, a biorepository of >300K DNA samples linked to de-identified medical records and evaluated genome-wide and imputed HLA class I and II associations with irAE risk. Methods: We identified 1,472 ICI-treated BioVU subjects: 428 with ≥ 1 irAE, and 1044 with no irAEs ≤ 6 months from last ICI treatment. Genotyping was performed by Illumina MEGAEX array. Records were screened for use of irAE therapies ( e.g. systemic corticosteroids, infliximab, levothyroxine) after ICI treatment, with chart adjudication. Association tests were performed using Firth’s logistic regression adjusting for age, sex, ICI regimen, and 3 principal components to assess 1) HLA Class I and II alleles; 2) HLA evolutionary divergence; and 3) GWAS to evaluate total irAEs, organ-specific irAEs, or other specific irAEs (sample size permitting). Endocrine irAEs were excluded to be presented in a separate focused study. Results: In GWAS analyses, 53 SNPs and 23 SNPs were identified significantly (nominal p ≤ 5e-8) associated with GI and neuro-toxicity, respectively. We did not identify any significant HLA class I or II associations with irAE or organ-grouped irAEs, including most evolutionary divergence association tests. We noted marginal association (FDR=0.12, OR=6.85) of rheumatic irAEs with HLA-DRB1*10:01, an HLA class II allele with RA-specific epitope motif. Patients experiencing lung irAEs were more likely to have a high HLA class I and II evolutionary divergence sum (p = 0.013 and p=0.046, respectively). Assessment of associations with specific irAEs, validation of known associations with irAEs or autoimmune disorders, including polygenic risk scores, are underway. Conclusions: We had several SNP-irAE associations, though appropriate classification schemas to maximize power and detect genetic variation remain challenging. We will soon expand with 1,800 additional ICI-treated patients (n=~3,300 in toto), creating a robust resource for irAE genetic associations. [Table: see text]

Joint-related manifestations of leprosy: A case report

Leprosy is a chronic granulomatous disease in which the musculoskeletal system has been described as the third most commonly affected system. Leprosy infections may manifest with various autoimmune phenomena reminiscent of classic autoimmune diseases. Among the leprosy factors affecting the prognosis of the disease, early diagnosis was reported to be the most effective. A 46-year-old married woman was referred to the hospital with initial articular symptoms. The patient also had deep folds, increased thickness of the skin in the forehead area, and dryness of the skin with a progressive course. The finger deformities and swelling are certainly misleading, but they may constitute an unsuspected inaugural form of leprosy, especially in its lepromatous form. The skin smear and biopsy confirmed leprosy, and treatment consisting of multi-drug therapy, as suggested by the WHO, was prescribed for the patient. According to these findings, it seems that one of the major symptoms of leprosy is musculoskeletal involvement and rheumatological manifestations, which may obscure and mislead diagnostic and treatment plans.

Silencing of FCRLB by shRNA ameliorates MuSK-induced EAMG in mice

IntroductionMuscle specific kinase (MuSK) antibody positive myasthenia gravis (MG) often presents with a severe disease course and resistance to treatment. Treatment-refractory patients may respond to B cell depleting treatment methods. Our aim was to investigate whether inhibition of Fc receptor–like B (FCRLB) could effectively suppress autoimmunity without diminishing B cell counts in animal model of MG, a classical antibody-mediated autoimmune disease. MethodsExperimental autoimmune MG was induced in Balb/C mice with two s.c. immunizations with recombinant human MuSK in complete Freund's adjuvant. FCRLB was silenced with a lentiviral particle transported shRNA in myasthenic mice with a single i.p. injection during second MuSK-immunization. Control immunized mice received scrambled shRNA or saline. Mice were observed for clinical parameters for 28 days and at termination, anti-MuSK IgG, neuromuscular junction (NMJ) deposits, muscle AChR expression and lymph node B and T cell ratios were assessed by ELISA, immunofluorescence, immunoblotting and flow cytometry, respectively. ResultsFCRLB shRNA-treated mice showed no muscle weakness or weight loss at termination. Also, they exhibited higher grip strength and muscle AChR levels, lower anti-MuSK IgG and NMJ IgG/C3 levels than control mice. Flow cytometry analysis showed that ratios of major effector lymph node B and T cell populations were not altered by FCRLB silencing. However, regulatory T and CD19 + CD5+ B cell ratios were decreased in FCRLB shRNA-group. ConclusionOur results provide evidence regarding involvement and therapeutic value of FCRLB in MuSK-MG. Silencing of FCRLB appears to substantially inhibit antibody production without interfering with survival of major lymphocyte populations.

SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy

ObjectivesThe protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect...

Role of artesunate in autoimmune diseases and signaling pathways.

Artesunate (ART) is a derivative of artemisinin. Compared with artemisinin, ART has excellent water solubility, high stabilityand oral bioavailability. In this review, the application of ART in classic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosusand ulcerative colitis issummarized. ART exhibited similar or even better efficacy than other highly effective immunosuppressive agents, such as methotrexate and cyclophosphamide. In addition, ART exerts its pharmacological effects mainly by inhibiting the production of inflammatory factors, reactive oxygen species, autoantibodies andthe migration of cells to reduce damage to tissues or organs. Moreover, ARTwidely affected theNF-κB, PI3K/Akt, JAK/STATand MAPK pathways to exert pharmacological effects.

Circulating miRNAs drive personalized medicine based on subgroup classification in myasthenia gravis patients.

Myasthenia gravis (MG) is a classic autoimmune neuromuscular disease with strong clinical heterogeneity. The concept of subgroup classification was proposed to guide the precise treatment of MG. Subgroups based on serum antibodies and clinical features include ocular MG, early-onset MG with AchR antibodies, late-onset MG with AchR antibodies, thymoma-associated MG, MuSK-associated MG, LRP4-associated MG, and seronegative MG. However, reliable objective biomarkers are still needed to reflect the individualized response to therapy. MicroRNAs (miRNAs) are small non-coding RNA molecules which can specifically bind to target genes and regulate gene expression at the post-transcriptional level, and then influence celluar biological processes. MiRNAs play an important role in the pathogenesis of autoimmune diseases, including MG. Several studies on circulating miRNAs in MG have been reported. However, there is rare systematic review to summarize the differences of these miRNAs in different subgroups of MG. Here, we summarize the potential role of circulating miRNAs in different subgroups of MG to promote personalized medicine.

Tuning peptide specificity for T cell tolerance in Type 1 diabetes

Abstract Type 1 Diabetes (T1D) is a classical T-cell mediated autoimmune disease, and fundamental data have implicated insulin as the dominant autoantigen in T1D disease. In the NOD mouse model of T1D, notable studies have found that mice lacking native insulin expression but with an altered insulin sequence to maintain blood glucose levels are protected from insulitis and diabetes. Growing evidence also indicates how the insulin peptide is bound within MHC Class II (peptide register) is essential in determining the strength of interactions and recognition of autoreactive T-cells. We have uncovered a unique peptide binding characterized by the dominant insulin epitope InsB:9–23. The majority of InsB:9–23-specific CD4 T-cells in the periphery recognize insulin bound in the unusual register 3, and knocking in this single amino acid variation into just one copy of the insulin gene in NOD mice, confers protection against T1D. In addition, these mice were protected from T1D, even when treated with checkpoint inhibitor blockade, unlike their wild-type littermates. Introducing this superagonist epitope into the NOD mouse has allowed us to address several key questions surrounding pathways of peptide generation, presentation by MHC molecules, and recognition by auto-reactive pathogenic T cells. In addition, we have been able to model how central and peripheral tolerance mechanisms can be altered when major epitopes in the Insulin gene are mutated, allowing us to explore means of dominant tolerance to understand the potential for translation into treatments for T1D. Supported by grants from NIH (R01 DK133443-01A)

Actualización en esclerosis múltiple: manifestaciones clínicas, formas evolutivas y estudios paraclínicos

Multiple sclerosis is the classic autoimmune disease of the central nervous system. Besides geographical, genetic and environmental-related propensity, it has recently been confirmed that the most important risk factor for the development of the disease is infection by the Epstein-Barr virus. The classic diagnostic criteria of at least two episodes of neurological dysfunction disseminated in time and affecting different anatomical locations have been updated in recent decades, considering paraclinical techniques that allow early diagnosis and initiation of treatment, which results in a better prognosis of the illness. Current understanding is that the clinical forms of multiple sclerosis are part of a continuous spectrum in which relapses of the disease and progression of disability coexist to different degrees.

Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis

Primary biliary cholangitis (PBC) is a classic autoimmune disease due to the loss of tolerance to self-antigens. Bile acids (BA) reportedly play a major role in biliary inflammation and/or in the modulation of dysregulated immune responses in PBC. Several murine models have indicated that molecular mimicry plays a role in autoimmune cholangitis; however, they have all been limited by the relative failure to develop hepatic fibrosis. We hypothesized that species-specific differences in the BA composition between mice and humans were the primary reason for this limited pathology. Here, we aimed to study the impact of human-like hydrophobic BA composition on the development of autoimmune cholangitis and hepatic fibrosis. We took advantage of a unique construct, Cyp2c70/Cyp2a12 double knockout (DKO) mice, which have human-like BA composition, and immunized them with a well-defined mimic of the major mitochondrial autoantigen of PBC, namely 2-octynoic acid (2OA). 2OA-treated DKO mice were significantly exacerbated portal inflammation and bile duct damage with increased Th1 cytokines/chemokines at 8 weeks post-initial immunization. Most importantly, there was clear progression of hepatic fibrosis and increased expression of hepatic fibrosis-related genes. Interestingly, these mice demonstrated increased serum BA concentrations and decreased biliary BA concentrations; hepatic BA levels did not increase because of the upregulation of transporters responsible for the basolateral efflux of BA. Furthermore, cholangitis and hepatic fibrosis were more advanced at 24 weeks post-initial immunization. These results indicate that both the loss of tolerance and the effect of hydrophobic BA are essential for the progression of PBC.

Therapeutic Potential of Targeting the NLRP3 Inflammasome in Rheumatoid Arthritis.

NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a cytoplasmic multiprotein complex composed of the innate immune receptor protein NLRP3, the adapter protein apoptosis-associate speck-like protein containing a caspase recruitment domain (ASC), and the inflammatory protease cysteine-1. Pathogen-associated molecular patterns (PAMPs) or other endogenous danger-associated molecular patterns (DAMPs) activate the NLRP3 inflammasome. As part of the innate immune response, activated NLRP3 promotes GSDMD-dependent pyroptosis, and IL-1β and IL-18 are released during inflammation. Aberrantly activated NLRP3 is deeply involved in various inflammatory diseases. Due to its interaction with adaptive immunity. NLRP3 inflammation has increasingly received attention in autoimmune diseases. Rheumatoid arthritis (RA) is a classic autoimmune disease, which mainly causes bone and cartilage damage. Elevated levels of NLRP3 can be detected in the synovium of RA patients. NLRP3 overactivation is strongly associated with RA activity. Mouse models of spontaneous arthritis has shown that NLRP3/IL-1β axis is implicated in periarticular inflammation in RA. In this review, we describe the current understanding of NLRP3 activation in RA pathogenesis and dissect its impact on innate and adaptive immunity. We also discuss the potential application of specific inhibitors of NLRP3 to provide new therapeutic strategies for treating RA.

Undifferentiated Connective Tissue Disease: Comprehensive Review.

Undifferentiated connective tissue disease (UCTD) is characterized by the presence of clinical symptoms of a systemic autoimmune disease in addition to laboratory evidence of autoimmunity with the patients not fulfilling any of the widely used classification criteria for classic autoimmune diseases. The presence of UCTD as a separate entity versus an early stage of such diseases as systemic lupus erythematosus (SLE) or scleroderma has long been debated. Given the uncertainty regarding this condition, we performed a systematic review on the topic. UCTD can be subcategorized as evolving (eUCTD) or stable UCTD (sUCTD) based on its evolution towards a definable autoimmune syndrome. Analyzing the data from six UCTD cohorts published in the literature, we found that 28% of patients have an evolving course with the majority developing SLE or rheumatoid arthritis within 5-6years of the UCTD diagnosis. From the remaining patients, 18% do achieve remission. Published treatment regimens were similar to other mild autoimmune diseases with low-dose prednisone, hydroxychloroquine, and NSAID. One-third of patients did need immune suppressive medications. Importantly, the reported outcomes were excellent with survival rates of more than 90% over 10years. It has to be noted though that as data on patient related outcomes are not available to date, the exact impact of this condition on quality of life is unclear. UCTD is a mild autoimmune condition with generally good outcomes. There is still great uncertainty though regarding diagnosis and management. Going forward, consistent classification criteria are needed to advance UCTD research and eventually provide authoritative guidance on the management of the condition.

Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder

Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.

Myasthenia Gravis: Types, Diagnosis and Treatment

The classic autoimmune disease, myasthenia gravis (MG), is brought on by certain autoantibodies at the neuromuscular junction. A classic illustration of an antibody-mediated autoimmune illness is MG. Autoantibodies against the acetylcholine receptors are present in the majority of MG patients (AChRs). Muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin are among the less frequently found autoantibodies. The downregulation, destruction, functional blockage, or disruption of AChR clustering in the postsynaptic membrane are all ways in which these autoantibodies interfere with cholinergic transmission between nerve terminals and muscle fibres. Fatigable muscle weakness, which may affect the ocular, bulbar, respiratory, and limb muscles, is the primary clinical symptom of MG. Depending on the autoantibody's kind and whether a thymoma is present, there are different clinical symptoms. By changing the immune homeostasis processes that stop the onset of autoimmune disorders like MG, a number of medications, including immune checkpoint inhibitors, penicillamine, tyrosine kinase inhibitors, and interferons, may cause de novo MG. Keywords: myasthenia, gravis, diagnosis, treatment

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events

BackgroundImmune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs)...

The key player in the pathogenesis of environmental influence of systemic lupus erythematosus: Aryl hydrocarbon receptor.

The aryl hydrocarbon receptor was previously known as an environmental receptor that modulates the cellular response to external environmental changes. In essence, the aryl hydrocarbon receptor is a cytoplasmic receptor and transcription factor that is activated by binding to the corresponding ligands, and they transmit relevant information by binding to DNA, thereby activating the transcription of various genes. Therefore, we can understand the development of certain diseases and discover new therapeutic targets by studying the regulation and function of AhR. Several autoimmune diseases, including systemic lupus erythematosus (SLE), have been connected to AhR in previous studies. SLE is a classic autoimmune disease characterized by multi-organ damage and disruption of immune tolerance. We discuss here the homeostatic regulation of AhR and its ligands among various types of immune cells, pathophysiological roles, in addition to the roles of various related cytokines and signaling pathways in the occurrence and development of SLE.

A Comparative Study of Mixed Connective Tissue Disease and Overlap Syndromes – A Single-Center Study from India

Introduction: Mixed connective tissue disease (MCTD) a classical overlap syndrome with four different defining criteria. The present study attempts to compare the clinical features and autoantibodies for MCTD and overlap syndromes. Methods: In this observational study from October 2018 to August 2020, we included all the patients of MCTD and overlap syndromes. Alarcon–Segovia criteria was used as defining criteria for MCTD patients while the patients meeting diagnostic criteria for more than 1 of 6 classical autoimmune rheumatic diseases were selected in the overlap syndromes group. We compared their clinical features, laboratory parameters, and autoantibody profiles. MS Excel, STATA were used for statistical analysis, and comparison between the groups was done with t-test, Chi-square test, and Wilcoxon rank sum test. P < 0.05 was considered as statistically significant. Results: The study consisted of 60 consecutive patients (MCTD, n = 30 and overlap syndromes, n = 30) with higher female population in both groups (90% in MCTD and 84% in the overlap syndromes group) compared to males. The incidence of fever (83.3% vs. 46.6%), weight loss (60% vs. 26.6%), trigeminal neuralgia (76.6% vs. 13.3%), and myositis (63.3% vs. 20.0%) was significantly higher in MCTD than overlap syndromes whereas the incidence of cough (66.6% vs. 90.0%) and dry mouth (20.0% vs. 53.3%) was higher in overlap syndromes than MCTD (P < 0.05). Anti-U1 RNP antibodies were seen in all MCTD (100.0%) patients while anti-Scl 70 antibodies (60%) and anti-ribosomal-p-protein antibodies (13.3%) were seen in overlap syndromes. Conclusion: Fever and weight loss, trigeminal neuralgia, and myositis were more common in MCTD than overlap syndromes. Anti-U1 RNP antibodies seen in MCTD while Anti-Scl 70 antibodies and anti-ribosomal-P antibodies were commonly were seen in overlap syndromes.

Активность кишечных карбогидраз у больных целиакией в зависимости от приверженности аглютеновой диете

Celiac disease is a classic autoimmune disease that triggers enterocyte damage and villous atrophy of the small intestine mucosa in genetically determined individuals in response to gluten-containing foods. Damage to the ultrastructure of epithelial cell membranes causes breakdown of the digestive transport conveyor, which disrupts the most important stage of the digestive transport conveyor – membrane digestion, which plays an important role in the final assimilation of nutrients. There is evidence of a correlation between the activity of intestinal carbohydrases and the degree of atrophy of the mucosa villi, which suggests that the activity of disaccharidases can serve as an indicator of the functional recovery of TTS in celiac disease. Objective: to assess the activity of intestinal carbohydrases in patients with celiac disease, depending on adherence to GFD. Materials and methods. We examined 109 patients with celiac disease, the diagnostic criterion for which was a combination of clinical symptoms, serological tests and histological data. The median age of the examined patients was 41.5 years (Q1–Q3: 30–55 years, Shapiro p-value < 0.01). There were 16 men (14.7%), median age 30; women – 93 (85.3%), median age 44 years. Depending on adherence to GFD, patients with celiac disease were divided into 3 groups: Group I – 39 patients with newly diagnosed celiac disease, Group II – 28 patients who consciously or unconsciously violated GFD, Group III – 42 patients who observed GFD from 6 months up to 15 years. The control group consisted of 30 practically healthy people comparable in age and sex. Their average age was 33.9 years (Q1–Q3: 24–35). All patients underwent esophagogastroduodenoscopy with a morphological and biochemical study of the mucosal tissue with a study of the activity of intestinal carbohydrases according to the method of A. Dalkvist modified by N.I. Belostotsky. The activity of disaccharidases of the small intestine mucosa was expressed in nanograms of glucose per milligram of tissue per minute (ng glucose/mg tissue × min). Results. In patients with newly diagnosed celiac disease, a decrease in the activity of glucoamylase glucoamylase (84.6%), maltase (87.2%) and sucrase (82.05%) (p < 0.01) is significantly more often detected compared to group III (glucoamylase – 33.3%; maltase – 45.2%; sucrase – 45.2%). Deficiency of all carbohydrases (glucoamylase, maltase, sucrase and lactase) was detected in 61.5% of patients. When comparing the indicators of carbohydrase activity in the groups of patients examined by us, it turned out that the average level of activity of glucoamylase, sucrase and maltase increased significantly more often as AGD was observed, however, their average values remained below the control level, which was less related to maltase. Thus, in group III, the level of maltase was 860 (644.5; 1413.5), and in the control group – 887.0 (854.5; 1146), which indicates a high ability of maltase to recover with strict adherence to GFD. The level of lactose activity in the studied groups of patients with different adherence to GFD did not differ significantly and was significantly lower than that in the control group, which indicates the presence of lactase deficiency in patients, which is difficult to correct by GFD. Conclusion. Based on the results of the work, it can be concluded that patients with celiac disease observing strict AHD are shown to study the activity of small intestine carbohydrases to assess the degree of recovery of the functional capabilities of the mucosa.