Severe combined immunodeficiency diagnosis and genetic defects.

Severe combined immunodeficiency (SCID) is a rare and life-threatening genetic disorder that severely impairs the immune system's ability to defend the body against infections. Often referred to as the "bubble boy" disease, SCID gained widespread recognition due to the case of David Vetter, a young boy who lived in a sterile plastic bubble to protect him from germs. SCID is typically present at birth, and it results from genetic mutations that affect the development and function of immune cells, particularly T cells and B cells. These immune cells are essential for identifying and fighting off infections caused by viruses, bacteria, and fungi. In SCID patients, the immune system is virtually non-existent, leaving them highly susceptible to recurrent, severe infections. There are several forms of SCID, with varying degrees of severity, but all share common features. Newborns with SCID often exhibit symptoms such as chronic diarrhea, thrush, skin rashes, and persistent infections that do not respond to standard treatments. Without prompt diagnosis and intervention, SCID can lead to life-threatening complications and a high risk of mortality. There are over 20 possible affected genes. Treatment options for SCID primarily involve immune reconstitution, with the most well-known approach being hematopoietic stem cell transplantation (HSCT). Alternatively, gene therapy is also available for some forms of SCID. Once treated successfully, SCID patients can lead relatively normal lives, but they may still require vigilant infection control measures and lifelong medical follow-up to manage potential complications. In conclusion, severe combined immunodeficiency is a rare but life-threatening genetic disorder that severely compromises the immune system's function, rendering affected individuals highly vulnerable to infections. Early diagnosis and appropriate treatment are fundamental. With this respect, newborn screening is progressively and dramatically improving the prognosis of SCID.

The Clinical Utility of Food Addiction: Characteristics and Psychosocial Impairments in a Treatment-Seeking Sample.

Little is known about the characteristics of individuals seeking treatment for food addiction (FA), and the clinical utility of FA has yet to be established. To address these gaps, we examined (i) the demographic, eating pathology, and psychiatric conditions associated with FA and (ii) whether FA is associated with psychosocial impairments when accounting for eating-related and other psychopathology. Forty-six patients seeking treatment for FA completed self-report questionnaires and semi-structured clinical interviews. The majority of the sample were women and self-identified as White, with a mean age of 43 years. Most participants (83.3%) presented with a comorbid psychiatric condition, most commonly anxiety and mood disorders, with a mean of 2.31 comorbid conditions. FA was associated with binge eating severity and anxiety symptoms, as well as psychological, physical, and social impairment. In regression analyses controlling for binge eating severity, food cravings, depression, and anxiety, FA remained a significant predictor only of social impairment. Taken together, the results suggest that individuals seeking treatment for FA are likely to present with significant comorbid conditions, in particular anxiety disorders. The results of the present research provide evidence for the clinical utility of FA, particularly in explaining social impairment.

Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation.

Almost 70 years after establishing the concept of primary immunodeficiency disorders (PIDs), more than 320 monogenic inborn errors of immunity have been identified thanks to the remarkable contribution of high-throughput genetic screening in the last decade. Approximately 40 of these PIDs present with autoimmune or auto-inflammatory symptoms as the primary clinical manifestation instead of infections. These PIDs are now recognized as diseases of immune dysregulation. Loss-of function mutations in genes such as FOXP3, CD25, LRBA, IL-10, IL10RA, and IL10RB, as well as heterozygous gain-of-function mutations in JAK1 and STAT3 have been reported as causative of these disorders. Identifying these syndromes has considerably contributed to expanding our knowledge on the mechanisms of immune regulation and tolerance. Although whole exome and whole genome sequencing have been extremely useful in identifying novel causative genes underlying new phenotypes, these approaches are time-consuming and expensive. Patients with monogenic syndromes associated with autoimmunity require faster diagnostic tools to delineate therapeutic strategies and avoid organ damage. Since these PIDs present with severe life-threatening phenotypes, the need for a precise diagnosis in order to initiate appropriate patient management is necessary. More traditional approaches such as flow cytometry are therefore a valid option. Here, we review the application of flow cytometry and discuss the relevance of this powerful technique in diagnosing patients with PIDs presenting with immune dysregulation. In addition, flow cytometry represents a fast, robust, and sensitive approach that efficiently uncovers new immunopathological mechanisms underlying monogenic PIDs.

Group therapy for excoriation disorder: Psychodrama versus support therapy.

BACKGROUND: Excoriation disorder (ED) is characterized by recurring excoriation of the skin resulting in tissue damage, usually associated with emotional deregulation. Psychotherapy is a valuable treatment; however, no studies emphasize the patients' interactional aspect, nor the potential benefit of group treatment. METHODS: We recruited a convenience sample of 38 individuals with ED according to DSM-5 criteria, in which 19 individuals proceeded to treatment, 10 with psychodrama group therapy (PGT), and 9 with support group therapy (SGT) in an open pilot study. RESULTS: The entire sample presented improvement of skin excoriation on both self-report and clinician rating and improvement of social adjustment; however, there was no difference between groups (ie, time × group interaction). Also, there was no relevant change for anxiety, depression, or emotional regulation throughout treatment. Emotional deregulation was associated with excoriation severity as well as depression, anxiety, and social maladjustment, both at the beginning and end of treatment. CONCLUSIONS: Although both groups showed improvement of skin picking, the results contradict our primary hypothesis that PGT would have a superior efficacy to SGT for patients with ED. The findings encourage future studies of group interventions for ED in larger samples with a focus on emotional regulation enhancement.

"There is no way to avoid the first bite": A qualitative investigation of addictive-like eating in treatment-seeking Brazilian women and men.

There has been polarizing debate on addictive-like eating in recent years. To move toward valid definition and measurement of this construct, qualitative research describing individuals' experiences is needed. The present study explored how Brazilian men and women define and experience addictive-like eating. Interviews were conducted with 7 men and 8 women (Mage = 46.6 years, MBMI = 35.43 kg/m2) seeking treatment for addictive-like eating. Thematic analysis of interviews identified three saturated, overarching themes describing participants' conceptualizations of the (1) characteristics, (2) causal factors, and (3) consequences of addictive-like eating. Lack of control was a key characteristic of addictive-like eating described by all participants. A causal factor which most participants described was emotional eating. Consequences included emotional, interpersonal, occupational, and health-related impairments which appeared primarily related to weight gain, rather than to the pattern of addictive-like eating itself. These results are largely consistent with those of previous qualitative studies. Importantly, the symptoms described by our participants and in previous qualitative studies may be inadequately captured by existing self-report questionnaires designed to assess addictive-like eating. To address this potential limitation, we provide recommendations for assessing the full range of possible addictive-like eating symptoms.

Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

NEWBORN SCREENING FOR SEVERE COMBINED IMMUNODEFICIENCIES USING TRECS AND KRECS: SECOND PILOT STUDY IN BRAZIL. / TRIAGEM NEONATAL DE IMUNODEFICIÊNCIAS GRAVES COMBINADAS POR MEIO DE TRECS E KRECS: SEGUNDO ESTUDO PILOTO NO BRASIL.

OBJECTIVE: To validate the quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) by real-time polymerase chain reaction (qRT-PCR) for newborn screening of primary immunodeficiencies with defects in T and/or B cells in Brazil. METHODS: Blood samples from newborns and controls were collected on filter paper. DNA was extracted and TRECs, and KRECs were quantified by a duplex real-time PCR. The cutoff values were determined by receiver operating characteristic curve analysis using SPSS software (IBM®, Armonk, NY, USA). RESULTS: Around 6,881 samples from newborns were collected and TRECs and KRECs were quantified. The TRECs values ranged between 1 and 1,006 TRECs/µL, with mean and median of 160 and 139 TRECs/µL, respectively. Three samples from patients with severe combined immunodeficiency (SCID) showed TRECs below 4/µL and a patient with DiGeorge syndrome showed undetectable TRECs. KRECs values ranged from 10 to 1,097 KRECs/µL, with mean and median of 130 and 108 KRECs/µL. Four patients with agammaglobulinemia had results below 4 KRECs/µL. The cutoff values were 15 TRECs/µL and 14 KRECs/µL and were established according to the receiver operating characteristic curve analysis, with 100% sensitivity for SCID and agammaglobulinemia detection, respectively. CONCLUSIONS: Quantification of TRECs and KRECs was able to diagnose children with T- and/or B-cell lymphopenia in our study, which validated the technique in Brazil and enabled us to implement the newborn screening program for SCID and agammaglobulinemia.

OBJETIVO: Validar a quantificação de T-cell receptor excision circles (TRECs) e kappa-deleting recombination circles (KRECs) por reação em cadeia de polimerase (polymerase chain reaction, PCR) em tempo real (qRT-PCR), para triagem neonatal de imunodeficiências primárias que cursam com defeitos nas células T e/ou B no Brasil. MÉTODOS: Amostras de sangue de recém-nascidos (RN) e controles foram coletadas em papel-filtro. O DNA foi extraído e os TRECs e KRECs foram quantificados por reação duplex de qRT-PCR. O valor de corte foi determinado pela análise de Receiver Operating Characteristics Curve, utilizando-se o programa Statistical Package for the Social Sciences (SSPS) (IBM®, Armonk, NY, EUA). RESULTADOS: 6.881 amostras de RN foram analisadas quanto à concentração de TRECs e KRECs. Os valores de TRECs variaram entre 1 e 1.006 TRECs/µL, com média e mediana de 160 e 139 TRECs/µL, respectivamente. Três amostras de pacientes diagnosticados com imunodeficiência grave combinada (severe combined immunodeficiency, SCID) apresentaram valores de TRECs abaixo de 4/µL e um paciente com Síndrome de DiGeorge apresentou TRECs indetectáveis. Os valores de KRECs encontraram-se entre 10 e 1.097 KRECs/µL, com média e mediana de 130 e 108 KRECs/µL, e quatro pacientes com diagnóstico de agamaglobulinemia tiveram resultados abaixo de 4 KRECs/µL. Os valores de corte encontrados foram 15 TRECs/µL e 14 KRECs/µL, e foram estabelecidos de acordo com a análise da Receiver Operating Characteristics Curve, com sensibilidade de 100% para detecção de SCID e agamaglobulinemia, respectivamente. CONCLUSÕES: A quantificação de TRECs e KRECs foi capaz de diagnosticar crianças com linfopenias T e/ou B em nosso estudo, validando a técnica e dando o primeiro passo para a implementação da triagem neonatal em grande escala no Brasil.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.

Depressão em pacientes com HIV/AIDS / Depression in patients with HIV/AIDS

Objetivo: investigar a prevalência de transtorno depressivo maior em pacientes com HIV/Aids, de uma unidade de referência da doença em Belém, Pará; descrever aspectos sócio-demográficos e clínicos; pesquisar se a terapia anti-retroviral e imunodeficiência estavam associados ao transtorno, assim como descrever os sintomas depressivos dos quadros identificados. Método: pesquisa transversal de prevalência em amostra de 115 indivíduos; aplicaram-se questionários para depressão (MINI, Inventário de Depressão de Beck e Escala Hospitalar de Ansiedade e Depressão). Resultados: não houve predomínio por sexo; 74.8% (86/115) dos entrevistados pertenciam à faixa etária de 30 a 50 anos; 65.2% (75/115) declararam-se heterossexuais; possuíam ensino fundamental incompleto 39.1% (45/115); recebiam algum benefício do governo 33.0% (38/115); residiam em Belém 58.3% (67/115); faziam uso da terapia anti-retroviral 76.5% (88/115) e apresentavam contagens de linfócitos T CD4+ abaixo de 350 células/mm3 46.1% (53/115). A prevalência de transtorno depressivo maior foi de 31.3% (36/115) e este não estava associado ao uso da terapia anti-retroviral, nem à imunodeficiência. Os sintomas depressivos mais freqüentes foram tristeza, auto-acusações, fadiga, irritabilidade, distúrbio do sono e preocupação somática. Conclusão: os resultados mostram uma elevada prevalência de transtorno depressivo maior em pacientes com HIV/AIDS.

Objectives: to investigate the prevalence of major depressive disorder in patients with HIV/Aids users of a reference center of this disease in Belém, Pará; to describe some sociodemographic and clinical aspects; to research if the antiretroviral treatment and imunodeficiency were associated with the disorder, as well as to describe the symptoms from those who had depression. Method: a cross-sectional study was made. The participants were assessed using questionnaires for depression (MINI, Beck Depression Inventory and Hospital Anxiety and Depression Scale). Results: in the end of the study, the sample was made by 115 individuals. There was no predominant sex; 74.8% (86/115) of the participants were between 30 and 50 years old; 65.2% (75/115) claimed that were heterosexual; had incomplete primary school 39.1% (45/115); received some benefit from the government 33.0% (38/115); lived in Belém 58.3% (67/115); were using antiretroviral treatment 76.5% (88/115) and had CD4+ T lymphocytes counts under 350 cells/mm3 46.1% (53/115). The prevalence of major depressive disorder was 31.3% (36/115) and this was not associated to the use of antiretroviral treatment, nor to imunodeficiency. The most frequent depressive symptoms were sadness, self-criticalness, fatigue, irritability, change in sleep patterns and somatic concern. Conclusion: the results show a high prevalence of major depressive disorder in patients with HIV/Aids

Depressão em portadores do vírus da imunodeficiência humana em uma Unidade de referência. Belém, Pará

Esta pesquisa foi realizada no período de novembro de 2007 a janeiro de 2009, com o objetivo de conhecer a prevalência de transtorno depressivo maior em amostra de pacientes acometidos pelo vírus da imonodeficiência humana atendidos na Unidade de Referência de Doenças Infecciosas e Parasitárias Especiais, na cidade de Belém, Pará...This research was conducted from November 2007 to January 2009, in order to know the prevalence of major depressive disorder in a sample of patients affected by the virus seen in human imonodeficiência Reference Unit Special Infectious and Parasitic Diseases in the city Belem, Para ..