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Lung cancer is the leading cause of cancer‐related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non‐small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min‐max) = 64.03 (45–83); 20 stage I–III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD‐1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD‐1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to report long‐term follow‐up of our pediatric and adult patients with DCLRE1C (DNA cross‐link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID). Methods: Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls. Results: Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B‐ and T‐cell lymphopenia at the first admission. Recent thymic emigrants (RTE), Tnaive, Bnaive, CD56dimCD16+ cell ratios were significantly lower in the patients than in control; however, follicular helper T TFH and Th1 [interferon gamma (IFN‐γ)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow‐up times of transplant patients was 56 (9–67) months. Conclusion: Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1‐dominant immune response before and after HSCT. Increased IFN‐γ and TFH cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long‐term follow‐up of these patients after HSCT will help to better understand the disease and its pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods: We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p <.001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score (p =.020, p =.003, p =.014, p =.013, p =.020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p =.012, p =.022, p =.011; respectively). Conclusion: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID‐19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid‐derived suppressor cells (MDSCs) in COVID‐19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID‐19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings—aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C‐reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty‐one patients with COVID‐19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets—polymorphonuclear MDSCs (PMN‐MDSCs) and monocytic MDSCs—by flow cytometric immunophenotyping, and PMN‐MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID‐19. Total MDSCs, PMN‐MDSCs, mature PMN‐MDSCs and monocytic MDSCs were significantly higher in patients with COVID‐19 compared with the healthy controls (P <.05). Only PMN‐MDSCs and their immature PMN‐MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C‐reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID‐19. These findings suggest that MDSCs play a role in the pathogenesis of COVID‐19, while PMN‐MDSCs, especially immature PMN‐MDSCs, are associated with the severity of the disease. [ABSTRACT FROM AUTHOR]

Increased levels of acute‐phase reactants and lymphopenia are predictors of disease severity in coronavirus disease 2019 (COVID‐19). This study aimed to investigate the role of apoptosis in the etiology of lymphopenia in patients with COVID‐19. This multicentered, prospective, and case‐control study was conducted with polymerase chain reaction (+) severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) patients, and an age–gender‐matched control group. Samples were taken at the time of diagnosis and analyzed via flow cytometry within 24 h. The participants' demographic data and initial laboratory tests were also recorded. In total, 33 patients with COVID‐19 (mean age = 45.4 ± 17.2) and 25 controls (mean age = 43.4 ± 17.4) participated in the study. All patients were identified as having mild (16), moderate (5), or severe (12) disease severity. Both early and late apoptotic cells in B and T lymphocytes were increased in all patients with COVID‐19 (p <.05). Early apoptotic (EA) B and T lymphocytes were also higher in severe cases compared to mild cases (p =.026). There was no significant difference between lymphopenia and apoptosis in patients with COVID‐19. However, patients with lymphopenia (n = 14) and severe COVID‐19 (p =.013) had increased EA T lymphocytes. This study's results show that B and T lymphocytes' apoptosis increases in patients with COVID‐19. In addition, enhanced T lymphocyte apoptosis is associated with disease severity in lymphopenic patients with COVID‐19. Highlights: One of the causes of lymphopenia in COVID‐19 disease is lymphocyte apoptosis.All lymphocyte subsets progress towards apoptosis with the disease severity.In those with lymphopenia, T cells seem to progress to more apoptosis than B.The IgG is markedly in a negative correlation with IgM in the lymphopenia group. [ABSTRACT FROM AUTHOR]

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper‐IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8‐deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. Methods: Peripheral blood ILC1‐3 subsets of 16 DOCK8‐deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post‐transplant DOCK8‐deficient patients (n = 12) by flow cytometry and real‐time qPCR. Sorted total ILCs from DOCK8‐ or STAT3‐mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL‐7, IL‐23, and IL‐12 by cell culture, flow cytometry, and phospho‐flow assays. Results: DOCK8‐deficient but not STAT3‐mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8‐deficient ILC1‐3 subsets had defective proliferation, expressed lower levels of IL‐7R, responded less to IL‐7, IL‐12, or IL‐23 cytokines, and were more prone to apoptosis compared with those of healthy controls. Conclusion: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8‐deficient patients to infections. [ABSTRACT FROM AUTHOR]

Background and Aims The appropriate treatment of pandemic H1N1 influenza which was first identified in April 2009 in Mexico is insufficient especially for immunocompromised patients. We aimed to evaluate the features and prognostic factors of the children with H1N1, especially immunocompromised ones, and whether intravenous immunoglobulin G ( IVIG) replacement could aid for a better outcome. Methods Twenty-one hospitalized children with laboratory-confirmed H1N1 were evaluated retrospectively. Data were extracted from files and electronic medical records. Results The median age was 37 (1-216) months; 62% of them were under 5 years of age and 71.4% had one or more underlying disorders. Main symptoms were high fever, cough, fatigue and vomiting. Lower respiratory tract manifestations were seen in 66.6% of children. Mortality rate was 4.7%. The patient who died had the lowest lymphocyte (100/mm3), thrombocyte (21 000/mm3) and highest blood urea nitrogen (87 mg/d L) levels. Fifty-eight percent of evaluated patients had one of the primary immunodeficiency disorders. Surprisingly, none of the six patients with primary immunodeficiency who are on regular IVIG replacement needed intensive care unit and died. Although median durations of cough, fever and hospitalization were lower, they did not change statistically according to get IVIG replacement regularly ( P = 0.47, 0.97, 0.09, respectively). Conclusion Our study is important while it is the first one that shows the course of primary immunodeficient children with H1N1 infection who were on regular IVIG replacement. A trial of high-dose IVIG may be a useful adjunctive therapy in severe H1N1 influenza, particularly in the immunocompromised patients. [ABSTRACT FROM AUTHOR]

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin (Ig) levels. Usually, this clinical picture resolves spontaneously by 3 yr of age. However, hypogammaglobulinemia persists until adolescence in some patients. In recent years, those patients have been classified as undefined/unclassified hypogammaglobulinemia (UCH). We aimed to evaluate the clinical and immunologic features of patients with THI and UCH considering age of recovery and to assess relationships between hypogammaglobulinemia, infections, and allergic manifestations. We reviewed the medical records of children followed with a diagnosis of hypogammaglobulinemia from 2001 to 2007. Patients with decreased levels (<2 s.d.) of one or more major Ig isotypes (IgG, IgA, IgM) with normal antibody responses and lymphocyte subpopulations were included (n = 374). Those patients whose Igs normalized during the follow-up period were classified as THI and the others as UCH. The THI group consisted of 71 patients (27 females, 44 males) with a mean recovery age of 68.87 ± 36.5 months. About 95% of patients with THI recovered before 10 yr of age. The UCH group consisted of 303 patients (105 females, 198 males) with a mean age at diagnosis of 52 ± 42 months. The most common presenting manifestations in the THI and UCH groups were upper respiratory tract infections (URTIs), lower respiratory tract infections, and asthma (42%, 50%, and 52% in the THI group vs. 39%, 53%, and 55% in the UCH group, respectively). In the THI group, the prevalence of atopic disease was related to age and found to be increased markedly after 44 months. In all patients, the prevalence of asthma was independently and positively associated with family history of atopy and age, whereas it was negatively associated with recurrent URTIs. Patients with THI and UCH have similar clinical and immunologic features. The normalization of Igs may be delayed in a majority of the patients with hypogammaglobulinemia. This observation may be a contribution to the classical definition and diagnostic criteria for THI. [ABSTRACT FROM AUTHOR]

Infection of the eyelids confined to the preseptal space is relatively common but potentially serious. We report a child with cutaneous anthrax to remind that the interesting contagious cause be included in the differential diagnosis of the preseptal cellulitis. [ABSTRACT FROM AUTHOR]