Inflammation in common variable immunodeficiency is associated with a distinct CD8(+) response to cytomegalovirus.

BACKGROUND: Common variable immunodeficiency is the most common primary immunodeficiency. A subset of patients has debilitating inflammatory complications. OBJECTIVES: We investigated the role of cytomegalovirus (CMV), and the T-cell response targeted at this virus, in this inflammatory disease. METHODS: Phenotypic and functional assays were used to profile CMV-specific T cells in patients with common variable immunodeficiency with and without inflammatory complications. Highly sensitive immunohistochemistry was used to detect CMV antigens at sites of inflammation. RESULTS: Cytomegalovirus was significantly associated with inflammatory disease, which occurred in 31 of 43 (72%) virus-exposed patients and 8 of 31 (26%) naive patients (P = .0001). CMV pp65-NLVPMVATV epitope-specific CD8(+) T-cell frequencies were significantly elevated in inflammatory patients, but these cells did not show evidence of exhaustion, with low levels of programmed death-1 and high T-cell receptor avidity. Rather, they showed features consistent with high in vivo functionality and proliferative activity including reduced levels of the anti-inflammatory marker CD73 (1.67% of NLV(+) cells were CD73(+) vs 42.01% in noninflammatory patients; P = .004) and increased Ki-67 expression (37% vs 2% in noninflammatory patients; P < .0001). In vitro, the CMV-specific T cells showed high antigen-specific proliferative potential compared with cells from noninflammatory patients. By using sensitive immunohistochemistry, we detected for the first time viral antigen at the sites of inflammation, indicative of active viral replication. CONCLUSION: Our data strongly support a direct role for CMV and a hyperreactive CMV-specific immune response in the debilitating chronic inflammatory complications of common variable immunodeficiency.

Early warning system-related challenges in health sector: A qualitative content analysis study in Iran.

CONTEXT: Iran's health system has always faced many challenges in the field of disaster risk management. The establishment of early warning systems in countries has been identified as an important component of preparedness and risk reduction. AIMS: This study aims to extract the experiences of those involved in the field of risk management in relation to the challenges and problems of early warning system establishment in the Iran's health system. SUBJECTS AND METHODS: This was a qualitative study, which has been conducted using a content analysis method. Data were collected through semi-structured interviews with 16 individuals who had at least one disaster management experience at the emergency operation centers. Sampling was done purposefully. The data were then analyzed using the Grenheim method. RESULTS: Nine subcategories of data were analyzed that included legal vacancies, challenges related to protocols and guidelines, weaknesses in the prediction infrastructure, weaknesses in the communication infrastructure, poor coordination, scarcity of resources, inadequate education, information management challenge, and evaluation challenge, and three main categories were extracted that included policy challenges, infrastructure challenges, and management challenges that represented the issues experienced in establishing an early warning system in the Iranian health system. CONCLUSION: Policy-makers and managers of health system need to pay special attention to improve the legal framework and standard protocol, strengthening infrastructures, increasing management performance in the field of coordination, education, allocation of resources, flow of information, and evaluation system.