Autoantibodies In Peripheral Blood Research Articles

Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy

AbstractBackgroundAutoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD); however, whether autoantibodies in peripheral blood can be used as biomarkers has not been reported.MethodSerum samples were obtained from 767, 146, and 255 patients with AD, mild cognitive impairment (MCI), and other neurodegenerative diseases, respectively, and 518 healthy controls. Specific autoantibodies were measured using a custom‐made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states.ResultSeven candidate AD‐specific autoantibodies were identified, and a classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out‐performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001).ConclusionAD onset and progression are associated with an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy

Autoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

PEMPHIGOID GESTATIONIS : CASE REPORT AND REVIEW OF LITTERATURE

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180. First-line treatment is local corticosteroid therapy if local treatment fails, general corticosteroid therapy should be administered. The prognosis is good for mother and child, except that there is a risk of preterm delivery and of moderate fetal growth restriction. Management in a specialized setting is therefore necessary. Recurrence is possible during subsequent pregnancies. We report a case of PG identified in our department, with a review of literature about physiopathology, diagnosis and treatment of this rare pathology.

Dual IgA/IgG family plasmablast-derived mAbs from peripheral blood of individuals at risk for rheumatoid arthritis are polyreactive to autoantigens and intestinal bacteria

Abstract A wide array of data supports rheumatoid arthritis (RA) as a disease with mucosal origins, including presence of IgA RA-associated autoantibodies in peripheral blood and biomarkers of inflammation at mucosal sites. Individuals at-risk for developing RA, (serum autoantibody+, without joint disease), can be characterized by an expansion in dual-family IgA/IgG circulating plasmablasts. We examined the characteristics of mAbs generated from these plasmablasts in at-risk (n=4) and early RA (&amp;lt;1 year from diagnosis, n=2) subjects. The variable regions of the plasmablasts were sequenced and clonal families mapped. 94 total heavy and light chain sequences were cloned into a mouse IgG2a constant region. All 94 expressed mAbs bound RA-related citrullinated/uncitrullinated synovial targets in an antigen array, demonstrating polyreactivity. As these mAbs were derived from IgA-containing clonal families, we queried if they have commensal bacterial targets by exposing them to a human fecal bacterial pool. 61.7% of mAbs had bacterial targets, suggesting additional polyreactivity. Bound bacteria were 16S rRNA sequenced. Interestingly, 56.31% ±12.85 of bound bacteria were of families Lachnospiraceae/Ruminococcaceae. A smaller subset of Vh genes were utilized among bacterially reactive plasmablast mAbs as compared to the wider population, though mutations from germline remained static between groups. Specifically, mAbs utilizing IgHV4-4, V3-64, V3-66, and V3-74 were bacterially reactive, and mAbs utilizing IgHV4-39, V4-59, V3-33, and V3-43 were not bacterially reactive. This demonstrates a link between mucosal and systemic immune systems in RA, suggesting an early mucosal trigger for disease-specific autoantibody development.

Peripheral Blood Autoantibodies Against to Tumor-Associated Antigen Predict Clinical Outcome to Immune Checkpoint Inhibitor-Based Treatment in Advanced Non-Small Cell Lung Cancer.

BackgroundPeripheral blood biomarkers to immunotherapy have attracted more and more attentions owing to noninvasive nature. This study was designed to identify a panel of tumor associated autoantibodies (TAAbs) in plasma to predict the clinical outcome of ICIs-based treatment in advanced NSCLC patients and correlation between TAAbs and checkpoint inhibitor pneumonitis (CIP) would also be investigated.Materials and MethodsBaseline plasma was collected from patients with advanced NSCLC before receiving ICIs-based treatment. ELISA was used to detect concentration of autoantibodies. Clinical efficacy was evaluated according to RECIST v1.1.ResultsWe have identified a panel of five-TAAbs to predict responses of ICIs-based treatment in a discovery cohort (n = 37), and confirmed its predictive value in a validation cohort (n = 129). In the validation cohort, the positivity of this 5-TAAbs panel was significantly associated with better response (ORR: 44.4% vs. 13.6%, P < 0.001) and longer PFS (7.6 vs. 3.3m, P < 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, P = 0.004,PFS: 6.7 vs. 3.7m, P = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, P = 0.001, PFS: 6.2 vs. 3.0m, P = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, P = 0.345, PFS: NR vs. 10.48m, P = 0.146). In addition, the CIP incidence in patients with 5-TAAbs positive was significantly higher comparing to negative patients (20.4% vs. 5.9%, P = 0.015).ConclusionOur 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.

CLINICAL AND NEUROLOGICAL PECULIARITIES AND THE LEVEL OF AUTOANTIBODIES TO NEUROSPECIFIC ANTIGENS IN PATIENTS WITH CHRONIC HEMOBLASTOSIS

The purpose of this study was to determine the level of autoantibodies to neurospecific antigens and their relationship with clinical manifestations of the nervous system lesions in chronic hematological malignancies. Materials and methods. The study included 86 patients with chronic hemoblastosis divided into 3 groups: group 1 consisted of patients with chronic lymphoid leukaemia (n = 30), group 2 involved patients with chronic myeloid leukaemia (n = 30), group 3 included patients with multiple myeloma (n = 26). 21 inpatients of the neurological hospital without immunological and hematological disorders were selected as a control group. We investigated the anamnestic data on the presence of a clinical diagnosis of the nervous system lesions before and after the establishing a cancerous hematological diagnosis, carried out a complete neurological examination of the patients with chronic hematoblastosis to determine main neurological syndromes. The level of peripheral blood autoantibodies to neurospecific antigens was evaluated by the enzyme immunoassay. The level of circulating immune complexes was determined by the method of selective precipitation of antigen-antibody complexes. The findings of the study were statistically processes by using Microsoft Excel 2019 and IBM SPSS Statistics 26.0 software. The data obtained were processed by descriptive statistics methods. The study has demonstrated that encephalopathy (70%) and radiculopathy (40%) develop statistically significantly more often in the patients with chronic lymphoid leukaemia. The patients with chronic myeloid leukaemia are found to have encephalopathy (43%) and polyneuropathy (20%). The development of multiple myeloma is statistically significantly accompanied by the occurrence of radiculopathy (50%) and polyneuropathy (53%). Conclusion. The nervous system lesions are found considerably frequent in the patients with chronic hematological malignancies. The development of secondary encephalopathy in the patients with chronic lymphoid leukaemia may develop as a consequence of paraneoplastic syndrome due to the excessive production of cytokines and plasminogen activators. The predominance of radiculopathy in chronic myeloid leukaemia can be reliably explained by the high severity of the proliferative syndrome with a tendency to the production of localized chlorine, which can compress the corresponding roots of the peripheral nerves. However, peripheral lesions of nervous system are more typical for patients with multiple myeloma that may be due to hyperparaproteinemia combined with the chemotherapy of the underlying disease. Along with this, chronic lymphoid leukaemia and chronic myeloid leukaemia cause an increase in the circulating immune complexes level. Immunological changes indicate significant damage to nerve fibres and considerably rapid destruction of neurons in all forms of chronic hemoblastosis.

Platelet autoantibodies in the bone marrow of patients with immune thrombocytopenia

AbstractAutoantibodies cause platelet destruction in patients with immune thrombocytopenia (ITP); yet only 50% to 60% of patients have detectable platelet autoantibodies in peripheral blood. We hypothesized that in some ITP patients, platelet autoantibodies are sequestered in the bone marrow where pathological immune reactions target megakaryocytes or newly formed platelets. In this study, we modified the platelet glycoprotein-specific assay to test bone marrow aspiration samples for free platelet autoantibodies or antibodies bound to bone marrow cells in aspirate fluid from patients with ITP (n = 18), patients with nonimmune thrombocytopenia (n = 3), and healthy donors (n = 6). We found that 10 (56%) of 18 patients with ITP had autoantibodies in the bone marrow, including 5 (50%) of 10 with autoantibodies in bone marrow only, and 5 (50%) of 10 with autoantibodies in bone marrow and peripheral blood. In comparison, 6 (33%) of 18 ITP patients had autoantibodies in peripheral blood, most of whom (5 [83%] of 6) also had autoantibodies in bone marrow. Bone marrow autoantibodies were not detected in patients with nonimmune thrombocytopenia or healthy donors; however, peripheral blood autoantibodies were detectable in 1 (33%) of 3 patients with nonimmune thrombocytopenia. The sensitivity of platelet autoantibodies for the diagnosis of ITP increased from 60% (peripheral blood testing) to 72% (peripheral blood and bone marrow testing). Immune reactions limited to the bone marrow may be characteristic of certain subsets of ITP patients.

Noninvasive detection of gastric cancer.

Gastric cancer (GC) is the fifth most common cancer and the third common cause of cancer death worldwide. Endoscopy is the most effective method for GC screening, but its application is limited by the invasion. Therefore, continuous efforts have been made to develop noninvasive methods for GC detection and promising results have been reported. Here, we review the advances in GC detection by protein and nucleic acid tumor markers, circulating tumor cells, and tumor-associated autoantibodies in peripheral blood. Some potential new noninvasive methods for GC detection are also reviewed, including exhaled breath analysis, blood spectroscopy analysis and molecular imaging.

Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies.

Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.

Seroprevalence of n-methyl-d-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients

N-methyl-D-aspartate glutamate receptors (NMDA-R) play a key role in learning and memory. Therefore, they may be involved in the pathophysiology of dementia. NMDA-R autoantibodies directed against the NR1a subunit of the NMDA-R, which were first identified as a specific marker for a severe form of encephalitis, cause a decrease in NMDA-Rs, resulting in cognitive impairment and psychosis. We examined the prevalence of NR1a NMDA-R autoantibodies in the serum and cerebrospinal fluid (CSF) of 24 patients with Alzheimer's disease (AD), 20 patients with subcortical ischemic vascular dementia (SIVD), and 274 volunteers without neuropsychiatric disorder. The latter cases showed an association of seropositivity with age. Notably, the overall seroprevalence was not statistically different between dementia patients and matched controls. Further analysis of the patient samples showed that four patients with AD and three patients with SIVD had positive NMDA-R IgM, IgG, and/or IgA autoantibody titers in serum. These patients suffered from psychosis (with the exception of one case). CSF samples were negative for NMDA-R autoantibodies. We conclude that the seroprevalence of NMDA-R-directed autoantibodies is age-related. It has to be clarified by larger studies whether NMDA-R autoantibodies in peripheral blood may predispose patients with AD and SIVD to susceptibility for psychotic episodes if disturbances of blood-brain-barrier integrity occur.

Oral lichenoid drug reaction with autoantibodies in peripheral blood: Case report

A 51-year-old man complained of oral roughness and pain. At the age of 49 years, he was admitted for 8 months for bipolar emotional disorder. Oral administration of lithium carbonate was started. Extensive, hemorrhagic, erythema-mixed white lace-like patches were noted on the lip, buccal mucosae, and lingual margins. On biopsy, all lesions were consistent with oral lichen planus. A drug lymphocyte stimulation test showed a positive reaction to lithium carbonate. Blood examination revealed marked increases in the peripheral blood levels of antinuclear antibodies. To relieve the symptoms, the systemic administration of prednisolone was performed while continuing the lithium carbonate.

Pemphigoïde gravidique

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180. First-line treatment is local corticosteroid therapy; if local treatment fails, general corticosteroid therapy should be administered. The prognosis is good for mother and child, except that there is a risk of preterm delivery and of moderate fetal growth restriction. Management in a specialized setting is therefore necessary. Recurrence is possible during subsequent pregnancies.

Is adenomyosis an immune disease?

Adenomyosis is characterized as ectopic endometrial tissues within the myometrium in the uterus. The only difference between adenomyosis and endometriosis is the site of endometriotic tissues: inside or outside of the uterus. It is well known that endometriosis is frequently associated with various autoimmune phenomena. This short review covers various aspects of the immune cascade found in adenomyosis. In adenomyosis, a series of immune responses is activated, including changes in both cellular and humoral immunity, i.e. a strong expression of cell surface antigens or adhesion molecules, an increased number of macrophages or immune cells, and deposition of immunoglobulins and complement components. Furthermore, the disease exhibited high frequency of autoantibodies in peripheral blood. Thus, an immunological 'vicious circle' is formed in the endometrium in adenomyosis. Endometrial cells seem to be under immunological stress, protecting themselves by exposing heat shock proteins. It is concluded that the endometrial environment in adenomyosis differs widely from that in normal fertile women. These abnormal immune responses might be involved in poor reproductive performance in adenomyosis.

Immunological responses to maxillary on-lay allogeneic bone grafts.

4 patients with severely resorbed maxillae underwent rehabilitation with on-lays of allogeneic femoral head bone grafts, titanium implants (Brånemark System) and fixed prostheses. Donors and recipients were matched according to blood groups (ABO/Rh). Potential immunological responses were monitored by determining autoantibodies in peripheral blood, and inflammatory reactions in the recipient site. Biopsies from the bone graft 6 months after grafting showed vital bone. After a mean observation period of 19.5 months, 22 of 23 implants were osseointegrated. None of the investigated autoantibodies were detected in peripheral blood, and there was no local inflammatory response. Allogeneic bone grafts in combination with titanium implants can be used in reconstruction of edentulous severely resorbed maxillae without immunological reactions directed against the graft.