Presence Of Autoimmune Markers Research Articles

ПОСТ-COVID-19 ІНТЕРСТИЦІЙНІ ЗАХВОРЮВАННЯ ЛЕГЕНЬ ЯК ПРОЯВ ПОСТКОВІДНОГО СИНДРОМУ

The aim was to study the clinical features of post-COVID-19 interstitial lung disease (ILD) and to determine the prospects for the use of the antifibrotic drug nintedanib in patients with moderate and severe COVID-19. Material and methods. A prospective cohort study was conducted in 266 patients (≥ 18 years old) with moderate and severe COVID-19 who were hospitalized and discharged after treatment at the Volyn Regional Clinical Hospital between September and November 2021. The study design included telephone contact with patients one year after hospital discharge to collect the complaints and history data related to postCovid syndrome. The patients with persistent respiratory symptoms were invited for an examination. A questionnaire, assessment of objective status, laboratory and functional tests were performed. The study included a group of patients (n = 25) with post-COVID-19 interstitial lung disease as a sequela of severe coronavirus infection. In all cases, interstitial pneumonia with a radiological pattern of chronic organizing pneumonia was established by computer tomography. All patients with post-COVID-19 ILD received glucocorticosteroid (GC) therapy with methylprednisolone 16 mg/day for 3–6 months with a gradual dose reduction until complete withdrawal. In addition, 9 patients with postCOVID-19 ILD received off-label antifibrotic therapy with the nintedanib 300 mg daily for 3 months. Statistical analysis was performed by means of SPSS Statistics 26 using the binomial test, the asymptotic T-test for the probability of success in two independent Bernoulli trial schemes, and the non-parametric Kolmogorov-Smirnov, Mann-Whitney U, and median tests. Results and discussion. In 9.4 % (n = 25) of patients post-COVID-19 ILD was diagnosed: 76 % (n = 19) — COVID-19 associated ILD; 16 % (n = 4) — systemic connective tissue disease (SCTD) triggered by COVID-19; 8% (n = 2) misdiagnosed pre-COVID-19 ILD. Radiological pattern of fibrosis-like lesions was established in 64% (n = 16); true fibrotic radiological pattern of pulmonary fibrosis (PF) — in 36 % (SCTD — 4 cases, other ILD — 2 cases). It was found that CPAP respiratory support did not significantly correlated with the presence of a radiological pattern of PF (p = 0.774) and the progression of postCOVID-19 ILD (p = 0.146). No significant correlation was found between the presence of a radiological pattern of PF and the gender of patients (p = 1.000 and p = 0.146, respectively) or age (p = 0.881 or p = 0.885). Despite the presence of autoimmune markers in number of cases and the diagnosis of SCTD, there was no correlation between PF pattern and SCTD ILD (p = 0.146 and p = 1.000). The use of nintedanib (n = 9) for 3 months in the remote period of severe COVID-19 disease did not changed the radiological pattern of PF (p = 1.000) and the progression of post-COVID-19 ILD (p = 0.180), same as the blood oxygen saturation post 6-minute walking test (p = 0.411 according to the median test and p = 0.329 according to the Mann-Whitney U test). There was no effect on the dyspnea index as well (p = 0.451 or p = 0.422). In our opinion, anti-fibrotic therapy in post-COVID-19 ILD should only be prescribed on individual basis for more than 3 months in the presence of a clinically significant PF radiological pattern. This recommendation requires further investigation. Key words: post-COVID-19 interstitial lung disease, post-covid syndrome, pulmonary fibrosis, nintedanib.

Markers of autoimmunity in immune thrombocytopenia: prevalence and prognostic significance

AbstractPrior studies have demonstrated an increased prevalence of autoimmune markers in patients with immune thrombocytopenia (ITP). Clinical experience has suggested that there may be an association between autoimmune markers and poor outcomes in ITP, but current guidelines do not encourage routine testing in these patients. We retrospectively assessed the prevalence of autoimmune markers in adult patients with ITP from our institutional database and used multiple logistic regression analyses to test for an association between autoimmune marker positivity and thrombotic events or clinical remission. We also assessed whether positivity for common autoimmune markers was associated with positivity for platelet autoantibodies. There was a high rate of autoimmune marker positivity in this population, with antinuclear antibody (65%), antithyroid peroxidase antibody (31%), and direct antiglobulin (29%) the most commonly found. Antithyroid peroxidase antibody positivity was associated with a lower probability of remission (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.79; P = .017). Lupus anticoagulant positivity was associated with a higher rate of thrombosis (OR, 8.92; 95% CI, 1.94-40.95; P = .005), and antinuclear antibody was strongly associated with thrombosis (P = .001). There was no relation between platelet autoantibody positivity and the presence of autoimmune markers. These results suggest that many patients with ITP have a state of immune dysregulation that extends beyond platelet autoantibodies and that certain autoimmune markers may be prognostically useful in this disorder.

Profiling Preexisting Antibodies in Patients Treated With Anti–PD-1 Therapy for Advanced Non–Small Cell Lung Cancer

Administration of anti-programmed cell death protein 1 (anti-PD-1) is now standard therapy in advanced non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors, including anti-PD-1, have not been assessed in patients with subclinical disease with advanced NSCLC, and no useful clinical biomarkers have been associated with immune-related adverse events (irAEs) among these patients treated with anti-PD-1. To assess the safety and efficacy of anti-PD-1 treatment in patients with subclinical disease with advanced NSCLC and with or without preexisting autoimmune markers, including rheumatoid factor, antinuclear antibody, antithyroglobulin, and antithyroid peroxidase; and to assess potential clinical biomarkers that may be meaningfully and conveniently associated with clinical benefit or with irAEs following anti-PD-1 treatment. This medical records analysis retrospectively evaluated 137 patients who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital in Japan between January 2016 and January 2018. Treatment efficacy and irAEs were evaluated along with candidate factors that may be associated with irAEs. Absence or presence of specific autoimmune markers and antibodies before treatment. Preexisting antibodies and autoimmune markers, progression-free survival (PFS), and irAEs. Of 137 patients with advanced NSCLC, 105 were men, the median age was 68 (range, 36-88) years, 99 underwent nivolumab monotherapy, 38 underwent pembrolizumab monotherapy, and 134 had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median PFS was 6.5 (95% CI, 4.4-12.9) months among patients with examined preexisting antibodies and 3.5 (95% CI, 2.4-4.1) months among patients without, suggesting significantly better prognosis in the former. The hazard ratio for disease progression or death in the presence of the examined preexisting antibodies was 0.53 (95% CI, 0.36-0.79; P = .002). The PFS was significantly longer among patients with any preexisting antibodies than among those without. The examined preexisting antibodies (48 patients [73%]) and rheumatoid factor (26 patients [39%]) were more common among patients who developed irAEs. Multivariate analysis indicated that the presence of the examined preexisting antibodies was independently associated with irAEs (odds ratio, 3.25; 95% CI, 1.59-6.65; P = .001). Skin reactions were more frequent among patients with preexisting rheumatoid factor (47% vs 24%, P = .02), whereas thyroid dysfunction was more frequent among patients with preexisting antithyroid antibodies (20% vs 1%, P < .001). The presence of the examined preexisting antibodies was associated with clinical benefit and with the development of irAEs in patients with NSCLC treated with nivolumab or pembrolizumab. Thus, the presence of these autoimmune markers may help determine the risk-benefit ratio for individual patients with NSCLC, maximizing therapeutic benefits while minimizing irAEs.

Role of Noninsulin Therapies in the Treatment of Type 1 Diabetes

Individuals with type 1 diabetes represent only ∼6% of all patients with diabetes in the United States and require characteristically complex treatment modalities (1). Autoimmune pancreatic β-cell destruction ultimately results in an absolute insulin deficiency, the presence of autoimmune markers, and little to no residual C-peptide (2,3). Additionally, pancreatic α-cell dysfunction is present, resulting in excess glucagon in both the fasting and postprandial states, and the gastric emptying rate is altered in many patients. Exogenous insulin serves as the foundation of therapy for type 1 diabetes and is commonly delivered via a multiple-dose regimen or an insulin pump. The two most common adverse effects associated with insulin use are hypoglycemia and weight gain. Recent data suggest that 68% of people with type 1 diabetes are overweight or obese and that severe hypoglycemia occurs at a rate of 9–20% (4). The latter complication is considered a limiting factor to achieving glycemic targets in the type 1 diabetes population. Indeed, the average A1C for adults ≥18 years of age with type 1 diabetes in the United States was 7.9% in 2015, a value well above the target of 7% recommended by the American Diabetes Association for most adult patients. Further complicating matters, diabetic ketoacidosis (DKA) occurs at a rate of 10% per year in some age-groups (4). Overall, these data suggest a need for adjunctive therapies for type 1 diabetes that reduce the risk for hypoglycemia and weight gain. While β-cell dysfunction is clearly a therapeutic focus for all types of diabetes, multiple other pathways of hyperglycemia present opportunities for alternate treatment modalities that may assist in achieving glycemic targets (5). The ideal pharmacotherapy regimen for a patient with type 1 diabetes would not only target the β-cell dysfunction, but also decrease blood glucose through hyperglycemic pathways independent of β-cell …

The Role of Neutrophils in Difficult-to-Treat Chronic Urticaria

RationaleNeutrophil predominance may be seen in the skin biopsies of difficult-to-treat chronic urticaria (dCU) patients. Data regarding the clinical course of CU patients based on the tissue infiltrate obtained from skin biopsy is limited. Our study compared serological and clinical parameters between neutrophilic-predominant urticaria (NU) and lymphocytic-predominant urticaria (LU) patients.MethodsFifty-one biopsies from dCU patients from 1999-2011 were reviewed. dCU was defined as treatment failure with at least 2 concurrent anti-histamines, use of oral steroids and/or immunomodulators. All biopsies were reviewed independently by 2 pathologists for cell count. Autoimmune markers (anti-nuclear antibody, anti-thyroid antibodies, rheumatoid factor, CU index), medications given (oral steroids, immunomodulators) and response to treatment were analyzed.ResultsSeventy-five percent (38/51) of patients were neutrophil predominant on biopsy. Forty-nine percent (25/51) had negative autoimmune markers. Sixty-seven percent (34/51) were on oral steroids and 18% (9/51) were on immunomodulators (dapsone, omalizumab, hydroxychloroquine, sulfasalazine). Twenty-seven percent (14/51) had complete resolution of symptoms, while 73% (37/51) had incomplete resolution. There was no statistically significant difference in the presence of autoimmune markers, resolution of symptoms, steroid and immunomodulator use between NU and LU patients.ConclusionsIn our study population, neutrophils were the predominant cell type on biopsy among dCU patients. However, this was not significantly associated with the presence of autoimmune markers or the use of steroids or immunomodulators. Further studies are needed to determine the influence of neutrophils and lymphocytes in dCU and its responsiveness to medical treatment. RationaleNeutrophil predominance may be seen in the skin biopsies of difficult-to-treat chronic urticaria (dCU) patients. Data regarding the clinical course of CU patients based on the tissue infiltrate obtained from skin biopsy is limited. Our study compared serological and clinical parameters between neutrophilic-predominant urticaria (NU) and lymphocytic-predominant urticaria (LU) patients. Neutrophil predominance may be seen in the skin biopsies of difficult-to-treat chronic urticaria (dCU) patients. Data regarding the clinical course of CU patients based on the tissue infiltrate obtained from skin biopsy is limited. Our study compared serological and clinical parameters between neutrophilic-predominant urticaria (NU) and lymphocytic-predominant urticaria (LU) patients. MethodsFifty-one biopsies from dCU patients from 1999-2011 were reviewed. dCU was defined as treatment failure with at least 2 concurrent anti-histamines, use of oral steroids and/or immunomodulators. All biopsies were reviewed independently by 2 pathologists for cell count. Autoimmune markers (anti-nuclear antibody, anti-thyroid antibodies, rheumatoid factor, CU index), medications given (oral steroids, immunomodulators) and response to treatment were analyzed. Fifty-one biopsies from dCU patients from 1999-2011 were reviewed. dCU was defined as treatment failure with at least 2 concurrent anti-histamines, use of oral steroids and/or immunomodulators. All biopsies were reviewed independently by 2 pathologists for cell count. Autoimmune markers (anti-nuclear antibody, anti-thyroid antibodies, rheumatoid factor, CU index), medications given (oral steroids, immunomodulators) and response to treatment were analyzed. ResultsSeventy-five percent (38/51) of patients were neutrophil predominant on biopsy. Forty-nine percent (25/51) had negative autoimmune markers. Sixty-seven percent (34/51) were on oral steroids and 18% (9/51) were on immunomodulators (dapsone, omalizumab, hydroxychloroquine, sulfasalazine). Twenty-seven percent (14/51) had complete resolution of symptoms, while 73% (37/51) had incomplete resolution. There was no statistically significant difference in the presence of autoimmune markers, resolution of symptoms, steroid and immunomodulator use between NU and LU patients. Seventy-five percent (38/51) of patients were neutrophil predominant on biopsy. Forty-nine percent (25/51) had negative autoimmune markers. Sixty-seven percent (34/51) were on oral steroids and 18% (9/51) were on immunomodulators (dapsone, omalizumab, hydroxychloroquine, sulfasalazine). Twenty-seven percent (14/51) had complete resolution of symptoms, while 73% (37/51) had incomplete resolution. There was no statistically significant difference in the presence of autoimmune markers, resolution of symptoms, steroid and immunomodulator use between NU and LU patients. ConclusionsIn our study population, neutrophils were the predominant cell type on biopsy among dCU patients. However, this was not significantly associated with the presence of autoimmune markers or the use of steroids or immunomodulators. Further studies are needed to determine the influence of neutrophils and lymphocytes in dCU and its responsiveness to medical treatment. In our study population, neutrophils were the predominant cell type on biopsy among dCU patients. However, this was not significantly associated with the presence of autoimmune markers or the use of steroids or immunomodulators. Further studies are needed to determine the influence of neutrophils and lymphocytes in dCU and its responsiveness to medical treatment.

Metabolic, immunological and clinical characteristics in newly diagnosed Asian diabetes patients aged 12-40 years.

To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia. Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore. The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA. Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.

Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5(+) subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5(+) B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5(+) B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5(+) population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5(+) peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Influence of age on clinical and immunological characteristics of newly diagnosed type 1 diabetic patients.

The aim of this study was to analyse the immunological and clinical characteristics of a group of patients at the onset of type 1 diabetes and to determine if these findings are age related. For this purpose, 68 newly diagnosed type 1 diabetes mellitus patients referred to our hospital between 1997 and 1999 were studied; 42 were adults (mean age 24+/-3.5 years) and 26 children (mean age 6.1+/-4 years). Autoantibody markers islet cell antibodies, glutamic acid decarboxylase antibodies (GADA) and tyrosine phosphatase antibodies (IA-2A), pancreatic reserve (glucagon test) and HbA1c were determined. Some clinical characteristics, such as mode of presentation and insulin requirements, were also analysed. Type 1 diabetes mellitus was found to be autoimmune in 83.8% of the patients and idiopathic in 16.2%, without significant differences between adults and children. In the whole autoimmune group, GADA was more prevalent in adults and IA-2A more frequent in children. On the other hand, adults showing autoimmune markers developed ketosis more frequently and needed higher insulin doses at diagnosis, while children did not exhibit clinically significant differences associated with the presence or absence of antibodies. In conclusion, in children the presence of autoimmune markers is not related to the mode of presentation or characteristics of type 1 diabetes. In adults, however, the autoimmune group presents with more-severe clinical disease than antibody negative patients. Age at onset seems to be an important parameter in the natural history of type 1 diabetes and must be taken into account in epidemiological or intervention studies.

Screening for Autoimmune Markers Is Unnecessary during Follow-up of Adults with Autoimmune Thrombocytopenic Purpura and no Autoimmune Markers at Onset

In an attempt to evaluate the frequency of autoimmune markers in autoimmune thrombocytopenic purpura (AITP) and to determine if autoimmune markers in patients with isolated AITP were associated with particular disease manifestations, we analyzed records of 122 consecutive adults with AITP. Twenty-nine patients (24%) had significant titers of one or several autoimmune markers at AITP onset. Among them, 16 (13%) had antinuclear antibodies. The presence of autoimmune markers did not correlate with presenting feature, response to treatment or long-term outcome of AITP. Six patients (5%) developed seven autoimmune diseases during follow-up, comprising systemic lupus erythematosus, an antiphospholipid syndrome, autoimmune haemolytic anemia (n = 2), Grave's disease, Hashimoto's disease and primary biliary cirrhosis. At AITP onset, three of these patients had isolated biological markers of the autoimmune disease they later developed. The annual average incidence rate of autoimmune diseases was 1% per patient-year in the entire group and 0.4% in the group of patients with no autoimmune markers at AITP onset. This low rate is probably due to careful assessment at diagnosis for concomitant overt autoimmune disease. We recommend extensive screening for autoimmune markers at AITP onset, and careful follow-up of patients with autoimmune markers. Routine screening for autoimmune markers during AITP follow-up is not necessary for patients with no autoimmune markers at AITP onset. Systemic lupus erythematosus (SLE) and other autoimmune disorders can complicate autoimmune thrombocytopenic purpura (AITP) or be diagnosed concomitantly with otherwise unremarkable AITP (1, 2). However, the frequency and prognostic value of isolated autoimmune markers (i.e. not associated with an autoimmune disorder), particularly antinuclear antibodies (ANA) at AITP onset or during follow-up is controversial (3-8). For example, the committee organized by George et al. (9) to write guideline on the diagnosis and treatment of AITP stated that the search for ANA and lupus anticoagulant were of "uncertain appropriateness at diagnosis and during follow-up". In an attempt to help practicians to make decisions, we analyzed the frequency of autoimmune markers and autoimmune disorders at onset and during the follow-up in 122 adults with AITP and no overt autoimmune disease at diagnosis. These consecutive patients were followed by the same physician for a mean period of 6 years, and had routine screening tests for autoimmune markers and disorders at onset, before steroid therapy, and regularly during follow-up.

Alpha-IFN treatment in HJCV CAH: Relationship with the presence of autoimmune markers: A Biglino, G Cariti, D Pini, M Depaoli, P Gioannini. Institute of Infectious Diseases, University of Turin, Italy

Alpha-IFN treatment in HJCV CAH: Relationship with the presence of autoimmune markers: A Biglino, G Cariti, D Pini, M Depaoli, P Gioannini. Institute of Infectious Diseases, University of Turin, Italy

Edta‐dependent pseudothrombocytopenia: A clinical study of 18 patients and a review of the literature

EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is the phenomenon of a spurious low platelet count due to the appearance of antibodies that cause platelet agglutination in blood anticoagulated with EDTA. We review here the clinical features of 18 patients with EDTA-PTCP treated in our hospital from 1984 to 1987 as well as those of 34 patients reported in the literature. This phenomenon appears more frequently in severely ill patients, in association with autoimmune, neoplastic, atherosclerosis-related, and liver diseases. In the majority of our patients, EDTA-PTCP appeared during hospitalization, indicating that the antibody is an acquired one. Neither splenomegaly nor the presence of autoimmune markers were features of this entity. Unlike true thrombocytopenias, EDTA-PTCP is associated with a normal mean platelet volume. Awareness of this entity is essential since EDTA-PTCP is frequently misdiagnosed and therefore incorrectly treated.

HBsAg seronegative chronic active hepatitis (CAH): Is the clinical course and outcome related to the presence of autoimmune markers?

HBsAg seronegative chronic active hepatitis (CAH): Is the clinical course and outcome related to the presence of autoimmune markers?