Concentrations Of Autoantibodies Research Articles

A Case of the Anti-aquaporine-4 Antibody-negative Neuromyelitis Optica Spectrum Disorders Associated with Atopic Disease with High Concentration of Anti-IgE Autoantibody and HyperIgEemia

We report a 70-year-old male patient with the sero-negative neuromyelitis optica spectrum disorders (NMOSD) associated with atopic disease (AD). He was diagnosed with allergic rhinitis at the age of 20. When he was 61 years old, he subacutely developed orthostatic hypotension, bilateral optic neuritis, quadriparesis, urinary retention, and constipation. The laboratory results revealed allergen-specific IgE positivity for cryptomeria japonica and hinoki, hyperIgEemia, and Th (helper T cell) 1 dominance. The serological tests for autoantibodies revealed negative anti-aquaporine 4 antibody, and high concentration of anti-IgE autoantibody (anti-IgE AAb). Cerebrospinal fluid was negative for anti-myelin-oligodendrocyte glycoprotein antibody and glial fibrillary acidic protein antibody. Fluid-attenuated inversion recovery on brain magnetic resonance imaging (MRI) showed high signal intensities in bilateral cerebral deep white matter. T2 weighted image on spine MRI showed longitudinally extensive high signal intensities in the spinal cord, specifically involving C1 vertebral level to conus medullaris. Intravenous methylprednisolone (IVMP) and plasma exchange resulted in partial improvement. Following the onset of NMOSD, he had relapse of NMOSD four times. In each episode, IVMP was to be partially effective with anti-IgE AAb reduction. Anti-IgE AAb may be a reasonable clinical indicator of increased disease activity in the sero-negative NMOSD associated with AD.

Autoimmune Hypothyroidism Associated with Helicobacter Pylori Infection

Objective: The study aimed to investigate the correlation between Helicobacter pylori (H. pylori) and thyroid autoimmunity. Material and Methods: To demonstrate the possible correlation between H. pylori infection and autoimmune hypothyroidism, 200 individuals were enrolled in this research (100 patients with active H. pylori infection and 100 healthy controls). All of them were tested for serum levels of thyroid hormones, thyroid stimulating hormone (TSH), and autoantibodies, as well as Helicobacter pylori-Immunoglobulin G (H. pylori-IgG) and cytotoxin-associated gene A-Immunoglobulin G (cagA-IgG) antibodies. Results: The study found that H. pylori infection was associated with higher levels of TSH, thyroperoxidase and thyroglobulin (TPO and TG) (p-value<0.000, 0.001 and 0.006, respectively) and a significant decrease in the levels of free-thyroid hormone (FT3 and FT4) (p-values=0.008 and 0.007 respectively) in patients compared with the control group. Moreover, using Pearson’s correlation tests, significant proportional correlations were found between H. pylori IgG and TSH (r=0.302, p-value=0.001), and a significant negative correlation was found between anti-H. pylori-IgG and with FT3 and FT4 (r=-0.261, p-value=0.003 and r=-0.260, p-value=0.003, respectively). Moreover, Spearman’s correlation results showed that H. pylori IgG was positively linked to TPO (r=0.531, p-value<0.001) and TG (r=0.320, p-value=0.001). Conclusion: The current investigation found that H. pylori infection was linked to higher concentrations of thyroid autoantibody and TSH and lower levels of thyroid hormones, suggesting that the bacterium may play a role in the development of subclinical autoimmune hypothyroidism.

No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation.

Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI. We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA-RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA-RI. The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (rsp = 0.51, p = 0.02). Assay levels were not elevated in CAA-RI patients (n = 6) compared to non-CAA controls (n = 20; p = 0.64). Literature review indicated only occasional presence of B-lymphocytes and plasma cells (i.e., antibody-producing cells), alongside the abundant presence of activated microglial cells, T-cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production. We were unable to reproduce the reported elevation of anti-Aβ autoantibody concentration in CSF of CAA-RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA-RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti-Aβ autoantibodies as a diagnostic biomarker for CAA-RI.

Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response.

Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response. Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead-based assays (Bio-Rad Bioplex 2200) and anti-C1q by enzyme-linked immunosorbent assay at the time of biopsy (baseline) and at 3, 6, and 12 months after biopsy. Clinical response was determined at 12 months. Proliferative LN (International Society of Nephrology/Renal Pathology Society class III/IV±V, n = 160) was associated with higher concentrations of anti-C1q, anti-chromatin, anti-double-stranded DNA (dsDNA), and anti-ribosomal P autoantibodies compared to nonproliferative LN (classes I/II/V/VI, n = 108). Anti-C1q and-dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti-C1q levels predicted complete response (area under the curve [AUC] 0.72; P = 0.002) better than baseline proteinuria (AUC 0.59; P = 0.21). Furthermore, all autoantibody levels except for anti-La/SSB decreased over 12 months in patients with proliferative, but not membranous, LN with a complete response. Baseline levels of anti-C1q and anti-dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti-C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in patients with proliferative LN.

PD1+CD4+ T cells promote receptor editing and suppress autoreactivity of CD19+CD21low B cells within the lower respiratory airways in adenovirus pneumonia

Human adenovirus (HAdV) pneumonia poses a major health burden for young children, however, factors that contribute to disease severity remain elusive. We analyzed immune cells from bronchoalveolar lavage (BAL) of children with HAdV pneumonia and found that CD19+CD21low B cells were significantly enriched in the BAL and were associated with increased autoantibody concentrations and disease severity. Myeloid cells, PD-1+CD4+ T helper cells and CD21low B cells formed tertiary lymphoid structures within the respiratory tracts. Myeloid cells promoted autoantibody production by expressing high amounts of B cell activating factor (BAFF). In contrast, PD-1+CD4+ T helper cells induced production of IgG1 and IgG3 antibodies but suppressed autoreactive IgGs by initiating B cell receptor editing. In summary, this study reveals cellular components involved in protective versus autoreactive immune pathways in the respiratory tract, and these findings provide potential therapeutic targets for severe HAdV lower respiratory tract infections.

Assessment of the effect of the CNTF gene rs1800169 polymorphism on serum dopamine levels in patients with vibration disease

Introduction. The modern stage in the study of vibration disease (VD) is characterized by a significant expansion of research in the field of investigating the role of neurotrophic factors that ensure the viability of the neuron and the functioning of the nervous system, as well as the identification of candidate genes encoding the processes underlying the development and course of the disease. An important regulator of brain dopamine neurons is ciliary neurotrophic factor (CNTF), which not only protects neurons from damage but regulates their functions. The functional significance of endogenous CNTF and the polymorphism of its genes to regulate the dopaminergic system are still not well understood. Materials and methods. Serum dopamine concentrations were determined by ELISA. Genotyping of the rs1800169 CNTF gene polymorphism was performed by real-time PCR. Results. In VD patients, an increase in the serum concentration of dopamine and autoantibodies to dopaminergic receptors has been established, which may indicate to changes in the corresponding neuronal systems. The distribution of genotype carriers for the rs1800169 CNTF gene polymorphism in VD individuals was: GG – 72 (0.81); AG – 15 (0.17); AA – 2 (0.02), and alleles – A – 2 (0.02); G – 159 (0.89) and corresponded to the Hardy-Weinberg equilibrium. Positive correlation relationship between frequency of detection of mutant allele A and dopamine level was revealed. The relative risk of exposure of carriers of the AG genotype of the rs1800169 polymorphic locus of the CNTF gene to the group of VD patients and dopamine levels above the reference values is 5.7 times more common than GG carriers. Limitations. The limitations of this work are due to small groups of employees. Conclusion. The association of the rs1800169 polymorphic locus of the CNTF gene with the serum dopamine concentration in VD patients was revealed. Mutant allele A is associated with an elevation in endogenous dopamine levels. Defective secretion of intracellular CNTF in the central nervous system appears to lead to increased dopamine production.

Uncommon triggers of insulin autoimmune syndrome: a case report

BackgroundInsulin autoantibody syndrome (IAS), or Hirata disease, is caused by high concentrations of insulin autoantibodies, which result in spontaneous, mainly post-prandial, hypoglycemic episodes. We report a case of a previously healthy 67-year-old man presenting with recurrent fasting hypoglycemia culminating in a diagnosis of insulin autoimmune syndrome linked to omeprazole and probably spices, namely, coriander, and ginger.Case presentationA previously healthy 67-year-old Sinhalese man presented with recurrent syncopal attacks for 3 months, which were found to be hypoglycemic episodes. He experienced mainly fasting hypoglycemic attacks, at a frequency gradually increasing to daily attacks. His cardiovascular, respiratory, abdominal, and neurologic examinations were normal. He was found to have insulin levels > 6000 mU/L and a post-polyethylene glycol insulin recovery of less than 9.5%. Contrast-enhanced computed tomography of the pancreas was normal. The diagnosis of insulin autoantibody syndrome was confirmed by testing for the insulin autoantibody level, yielding a level of > 300 U/mL. With regard to a possible trigger, he had a history of omeprazole intake for 2 weeks, 4 weeks prior to the onset of symptoms. He also consumed an herbal supplement containing coriander and ginger extracts daily for a period of 1 year, approximately 2 years prior to the onset of hypoglycemic attacks. He was commenced on prednisolone 30 mg daily, and hypoglycemic episodes responded dramatically, and thus he was tapered off corticosteroids.ConclusionOmeprazole-induced insulin autoantibody syndrome is likely in this patient; however, the known hypoglycemic effects of coriander and ginger make it worthwhile to consider a possible association with insulin autoantibody syndrome. In addition, this case report highlights the need to consider insulin autoantibody syndrome even in patients presenting with fasting hypoglycemic attacks.

Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE. MethodsWe performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity. ResultsWe observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = −0.530; p = 0.007) and anti-PmScl100 (r = −0.445; p = 0.03). ConclusionWe identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature.

Exploring serum α‑synuclein and its autoantibodies in essential tremor: implications for diagnosis and symptom correlations.

There is no definite biomarker for confirming the diagnosis of essential tremor (ET) or differentiating it from other diseases, particularly Parkinson's disease. The present study aimed to investigate the serum levels of the α-synuclein protein (α-syn) and its autoantibodies in patients with ET compared with healthy controls and its relation to motor and non-motor symptoms in patients with ET. Serum α-syn and its autoantibodies were measured in 32 patients with ET and 32 age- and sex-matched controls. Both groups were assessed using the non-motor symptoms scale, MoCA, Beck Depression Inventory, Hamilton Anxiety Rating Scale, and the Short Form 36 Health Survey Questionnaire. Tremor was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. The serum α-syn concentration in patients with ET was significantly lower than that in healthy controls (P<0.001), with a positive predictive value of 0.81 and a negative predictive value of 0.75, while the serum anti-a-syn autoantibody concentration was not significantly different between the two groups. There were no correlations between serum α-syn or its autoantibodies and patients' clinical characteristics. Furthermore, patients with ET had worse cognitive impairment, depression, anxiety, non-motor symptoms and quality of life. The serum α-syn concentration was lower in patients with ET than in controls, with favorable predictive values, suggesting that it could serve as a biomarker for ET diagnosis.

Doxycycline for the treatment of nodding syndrome: a randomised, placebo-controlled, phase 2 trial

Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment. In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913. Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups. Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections. Medical Research Council (UK). For the Luo translation of the abstract see Supplementary Materials section.

Assessment of glial fibrillary acidic protein and anti-glial fibrillary acidic protein autoantibody concentrations and necrotising meningoencephalitis risk genotype in dogs with pug dog myelopathy.

Pugs commonly present with thoracolumbar myelopathy, also known as pug dog myelopathy (PDM), which is clinically characterised by progressive signs involving the pelvic limbs, no apparent signs of pain and, often, incontinence. In addition to meningeal fibrosis and focal spinal cord destruction, histopathology has confirmed lymphohistiocytic infiltrates in the central nervous system (CNS) in a considerable number of pugs with PDM. Lymphohistiocytic CNS inflammation also characterises necrotising meningoencephalitis (NME) in pugs. This study aimed to investigate the potential contribution of an immunological aetiology to the development of PDM. The concentrations of glial fibrillary acidic protein (GFAP) in serum and CSF and of anti-GFAP autoantibodies in CSF were measured with an ELISA. In addition, a commercial test was used for genetic characterisation of the dog leukocyte antigen class II haplotype, which is associated with NME susceptibility. This study included 87 dogs: 52 PDM pugs, 14 control pugs, four NME pugs and 17 dogs of breeds other than pugs that were investigated for neurological disease (neuro controls). Anti-GFAP autoantibodies were present in 15 of 19 (79%) of the PDM pugs tested versus six of 16 (38%) of the neuro controls tested (p = 0.018). All 18 PDM pugs evaluated had detectable CSF GFAP. Serum GFAP was detected in two of three (67%) of the NME pugs and in two of 11 (18%) of the control pugs but not in any of the 40 tested PDM pugs. Male pugs heterozygous for the NME risk haplotype had an earlier onset of clinical signs (70 months) compared to male pugs without the risk haplotype (78 months) (p = 0.036). The study was limited bythe lack of healthy dogs of breeds other than pugs and the small numbers of control pugs and pugs with NME. The high proportion of PDM pugs with anti-GFAP autoantibodies and high CSF GFAP concentrations provide support for a potential immunological contribution to the development of PDM.

Autoantibodies to type I interferons in patients with systemic mastocytosis

Autoantibodies to type I interferons have been identified in association with a variety of inflammatory and autoimmune diseases. Type I interferons have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release. Whether autoantibodies to type I interferon are present in the sera of patients with SM, and if so, whether they correlate with characteristics of disease, is unknown. The purpose of this study was to determine whether autoantibodies to type I interferons are observed in the sera of patients with SM, and if so, whether they correlate with biomarkers of disease severity. We analyzed sera from 89 patients with SM for concentrations of autoantibodies to type I interferon by using a multiplex particle-based assay and signal neutralization capacity by using a STAT1 activity assay and then compared these measurements with those in a database of information on 1284 healthy controls. Our cohort was predominantly female (57.3%), with a median age of 56 years. Of the cohort members, 13 produced autoantibodies to IFN-β, 3 to IFN-ω, and 0 to IFN-α. None of the 13 sera demonstrated signal neutralization. Neither autoantibody concentration nor signaling inhibition measurements correlated with tryptase concentrations or D816V allele burden. Although a small subpopulation of patients with SM have autoantibodies to type I interferons, there was no correlation between autoantibody production and signaling inhibition. These data are consistent with the conclusion that autoantibodies to type I interferon do not play a significant role in the pathogenesis or severity of SM.

SEVERITY OF NEUROLOGICAL LONG-COVID SYMPTOMS CORRELATES WITH INCREASED LEVEL OF AUTOANTIBODIES TARGETING VASOREGULATORY AND AUTONOMIC NERVOUS SYSTEM RECEPTORS

Objective: The Long-COVID syndrome is characterized by a variety of physical, cognitive and psychological symptoms. Worldwide, at least 65 million people are thought to be affected, nevertheless there is still insufficient knowledge about the pathogenesis of long-COVID. Studies on the Long-COVID related myalgicencephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest autoimmune-related changes, for example the formation of autoantibodies against G protein-coupled receptors. Design and method: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). Autoantibodies towards the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA. Neurological disorders and fatigue were quantified by internationally standardized questionnaires including Chalder Fatigue Scale, Short-Form-36 Questionnaire and the CERAD Neurophysiological Assessment Battery. Results: The prevalence and concentrations of evaluated autoantibodies were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1∗10-9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R &lt;= -0.26, p &lt;= 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087). Conclusions: The present study shows that autoantibodies to GPCR are highly prevalent in patients with Long-COVID. These autoantibodies occur in healthy controls as well, but the prevalence is substantially lower. Concentrations of autoantibodies correlates to intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.

Medical Ozone: A Redox Regulator with Selectivity for Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone. The redox status of 80 patients was determined: antioxidant defenses, injury markers, two subjective variables (pain and disability), and levels of antibodies against cyclic citrullinated peptides were evaluated. Oxidative stress and clinical response to combined therapy with ozone was higher than in the case of RA. After medical ozone treatment, there was an increase in antioxidant defense and a decrease in injury markers as well as pain, disability, and autoantibody concentrations. Redox biomarkers were able to differentiate between both arthritic diseases and combined therapy with ozone (methotrexate + ozone), showing a therapeutic selectivity for RA in comparison with OA.

Folate receptor alpha autoantibodies in the serum of patients with relapsing–remitting multiple sclerosis (RRMS)

Multiple sclerosis (MS) is a potentially progressive, autoimmune neurologic disorder of the central nervous system (CNS), resulting from an autoimmune attack on central nervous system white matter. Folate deficiencies are linked to DNA instability and breakdown of phospholipid membranes and thus might affect myelin integrity. Folic acid exerts its effects through its receptors (FRs). Folate receptor alpha autoantibodies (FRAA) can block folate transport to the brain. Due to important role of folate in the pathogenesis of MS, in this project we aimed to study FRAA serum levels in patients with relapsing remitting multiple sclerosis (RRMS). Fifty-four patients with RRMS and 58 healthy individuals were enrolled in this study. Serum samples were collected from all participants and folate receptor alpha autoantibody (FRAA) serum concentration was measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that FRAA serum levels in patients with RRMS is 67.20±19.79ng/ml as compared to controls which was 37.32±13.26ng/ml. Significant increase in folate receptor autoantibody serum concentration was seen in patients with RRMS when compared to control group (P=0.007). The results showed that a high concentration of folate receptor autoantibody is associated with RRMS. We have also found that 85.18% (46/54) of patients with RRMS were positive for serum FRAA, whereas the prevalence in controls was only 46.55% (27/58). It is concluded that serum FRAA are more prevalent in RRMS patients than controls. The findings also suggest that FRAA might be involved in the pathophysiology of RRMS.

P-23 Insulin autoimmune syndrome possibly induced by Alpha-Lipoic acid

Abstract Introduction Insulin autoimmune syndrome (IAS) is a relative rare cause of hypoglycemia due to the presence of extremely high circulating insulin levels and elevated serum concentrations of autoantibodies to human insulin despite no prior exposure to exogenous insulin, insulin analogues or oral hypoglycemic agents. It is characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals in non-diabetic, non-acutely ill patients. Increasing the titer of insulin autoantibodies and immune reactive insulin occurs owing to both genetic influences and environmental triggers such as medication, genetic instability and other factors. It is associated with the use of drugs comprising sulfhydryl groups, such as methimazole, clopidogrel and alpha lipoic acid, mostly. Insulin autoantibodies appear a few weeks after the exposure of sulfhydryl radicals. Here, we summarize the case of IAS caused by drug administration. Clinical Case A 60-year-old female patient who has a history of migraine for 30 years was referred to our hospital for feeling of hunger, dizziness, sweating, tremor, and palpitations for 1 month. These symptoms had commenced episodically, soon after starting 600 mg/day of alpha lipoic acid. She was diagnosed with hypoglycemia based on a plasma glucose concentration of 31 mg/dL. There was no personal or family history of diabetes mellitus, or previous use of oral hypoglycemic drugs such as sulfonylureas or exogenous insulin. No abnormality was detected in the systemic examination. She had no smoking and alcohol abuse. Her regular medication was tricyclic antidepressant (amitriptyline). Laboratory results are presented in Table 1. On our evalution, the serum levels of insulin, C-peptide, and anti-insulin antibody titers were inappropriately elevated in the presence of hypoglycemia, confirming the diagnosis of hyperinsulinemic hypoglycemia. Thyroid function, human growth hormone, insulin growth factor-1 (IGF-1), and cortisol result were within normal limits. Screening for antinuclear factor, serum protein electrophoresis, serology for viral hepatitis, and other autoimmune diseases were negative. Insulinoma was excluded with computed tomography. In light of the above results, a diagnosis of IAS was made with possible alpha lipoic acid. Because, alpha lipoic acid was the only medication being taken associated with a sulfhydryl group. The patient was prescribed oral methylprednisolone (32 mg once daily), alpha lipoic acid was withdrawn. Hypoglycemia did not occur after methylprednisolone treatment of follow-up. Methylprednisolone treatment was tapered to 4 mg once daily within 2 months. The insulin, and anti-insulin antibody titers had decreased. Conclusion We report a rare case of IAS. Sulfhydryl group containing drugs such as alpha lipoic acid might induce or exacerbate hypoglycemia in patients with a history of IAS. For this reason, the use of alpha lipoic acid should be questioned in patients with IAS. Table 1. Laboratory test results

Acquired haemophilia A in paediatric patients: A retrospective French cohort of eight cases.

Acquired haemophilia A (AHA) is a rare haemorrhagic disease characterised by new-onset haemorrhagic symptoms associated with a dramatic decrease in factor VIII levels and an anti-factor VIII neutralising autoantibody concentration >0.6 Bethesda units. Elderly people are often affected, whereas children are rarely affected; the paediatric incidence reported in the literature is about 0.045 case/million/year. For some time, the paediatric standard of care has been that for adults, but clinicians have often reported poor outcomes. Here, we describe the largest retrospective paediatric AHA cohort assembled to date, including eight patients diagnosed in France from 2000 to 2020.

The role of medical and organizational measures in improving the quality of early detection and clinical examination of autoimmune thyroiditis among the population of the Republic of Belarus

Objective. To evaluate the role of medical and organizational measures in improving the quality of early detection and medical examination of autoimmune thyroiditis in the population of the Republic of Belarus.Materials and methods. The data of population statistics and the State register of persons affected by the Chernobyl catastrophe and other accidents on cases of thyroid pathology, as well as outpatient records of patients were analyzed. Epidemiological, statistical and sociological methods were used.Results. It was noted that different clinical and laboratory variants of autoimmune thyroiditis (AIT) are encountered in clinical practice. Subclinical AIT with sonographic signs of the disease but without diagnostic concentrations of antibodies to thyroid peroxidase (AB/TPO) and disturbances of its function is registered in 14.1 (6.0-24.4) %. AIT with diagnostic concentrations of autoantibodies to AB/TPO, with preserved thyroid function or hypothyroidism occurs in 22.5 (13.534.0) % of the cohort subjects. The frequency of combining AIT with nodular neoplasms of the thyroid increased by the 4th stage of screening and reached 20.7 (11.2-33.4) %.The reasons for different approaches to diagnosis were analyzed and measures to improve organizational and medical measures for early detection and dispensary treatment of patients with AIT were proposed: groups of persons at high risk of AIT and primary hypothyroidism (PHT) were identified, an algorithm for early detection and dispensary treatment was developed, etc.Conclusion. When making a decision to improve the quality of medical care to the population of the Republic of Belarus on early detection and medical examination of patients with AIT, it is necessary to take into account the timeliness of thyroid status studies in the population, compliance with the terms of dynamic observation for persons at high risk of AIT and PHT development, peculiarities of clinical and laboratory variants of AIT course.

Exploring the role of autoantibodies in Iraqi females with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy that affects 5-10% of women during their reproductive years. Clinicians characterize it by the occurrence of ovarian cysts, oligomenorrhea, amenorrhea, and either clinical or biochemical evidence of hyperandrogenism. Recent research suggests a potential link between autoantibodies and PCOS development. Aim of study: This study investigated the relationship between autoantibodies and Polycystic ovary syndrome (PCOS). Materials and methods: The study involved a total of 150 female participants diagnosed with PCOS, aged between 20 to 35, and a control group of 150 individuals. We utilized chemiluminescent immunoassays to measure Anti-thyroid antibodies thyroglobulin (TG) and thyroid peroxidase (TPO). We conducted IgM and IgG for anti-cardiolipin (ACL) and β-2 glycoprotein I (B2GPI) using the enzyme-linked immunosorbent assay (ELISA). To measure lupus (La), we employed coagulation time. To assess the serum levels of total antibodies Ig (M, G, A), Serum amyloid A (SAA), High-Sensitivity C-reactive protein (hs-CRP), and Procalcitonin (PCT), we used nephelometry methods. Results: In our findings, patients showed a significantly higher level of TPO autoantibodies (91.9±14.7) compared to the control group (12.4±5.1). This difference was highly significant (&lt;0.001). Similarly, we observed high levels of anti-TG antibodies in patients (50.4±10.3) compared to the control group (30.6±7.2). This points out the important role of both TPO and TG antibodies in this context. Moreover, the level of IgM for ACL was significantly higher in patients (19.2±4.2 AU/dl) than in controls (3.3±1.0 AU/dl). The level of IgG for ACL was also higher in patients (22.5±2.3 AU/dl) compared to controls (3.3±1.0 AU/dl). These increases in ACL antibodies in patients suggested a risk factor for the disease. Additionally, Serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) were significantly higher in patients, with measurements of 66±10.4 (AU/ml) and 55±12.5 (AU/ml) respectively, compared to controls who had measurements of 3.6±1.9 (AU/ml) and 2.3±0.98 (AU/ml) respectively, which was highly significant (&lt;0.001). Procalcitonin (PCT) was also highly significant in patients (40±6.3 AU/ml) compared to the control group (6.4±2.6 AU/ml). Lastly, the concentration of total IgG antibodies was significantly higher in patients (25.3±2.6 AU/dl) than in controls (4.3±1.0 AU/dl), with a significant difference (P=0.006). Conclusion: High concentrations of autoantibodies in patients suggest a risk factor and positive associations with the disease.

Effectiveness of a gluten-free diet on the autoantibody frequency of endocrine and neuron disorders in patients with celiac disease

Several possible associations between different types of autoimmune diseases have been reported, therefore this study aimed to investigate the relationship between celiac disease (CD) and some related autoimmune diseases by determining the effect of gluten on severity of these diseases. Two hundred blood samples were collected, 50 samples were withdrawn from healthy donors as a control group, 75 were collected from newly diagnosed (ND) CD patients, while the remaining blood samples (75) were obtained from the same patients after 4 months of gluten free diet (GFD) regime. Sera were separated to measure the level of anti-tissue transglutaminase IgA (tTG-IgA), anti-pituitary IgG, anti- thyroid peroxidase IgG (TPO- IgG), anti-islet IgG and anti-ganglioside IgG (IU/ml) by enzyme linked immunosorbent assay (ELISA). To analyze the results and compare between groups, GraphPad Prism was utilized. The results recorded high significant elevation (p&gt;0.0001) in the concentrations of all autoantibodies of both ND and GFD groups compared with their concentrations in the control group. Furthermore, after 4 months of GFD, all autoantibodies concentrations revealed highly significant decreases (p&gt;0.0001) as compared with ND. Regarding the correlation of all studied autoantibodies with anti tTG-IgA, only anti-ganglioside IgG levels were weakly correlated in pre-GFD treatment patients, meanwhile anti-ganglioside IgG and anti-pituitary IgG were also recorded weak correlations in post- GFD of CD patients. This study concluded that GFD helps to reduce the severity of endocrine and neuron autoimmune disorders in addition to CD, which have been proved by decreasing in the level of their diagnostic autoantibodies.