Paediatr Respir Rev. are at risk of developing bronchiectasis, ILD occurs in some forms of PAD much more generally than others, suggesting that unique but poorly understood immunological factors underlie development of this complication. Importantly, ILD can have earlier onset and may worsen survival more than bronchiectasis. Further efforts to understand the pathogenesis of lung disease in PAD will provide vital information for the most effective methods of analysis, monitoring, and treatment of these individuals. Keywords: common variable immunodeficiency, CVID, granulomatous interstitial lung disease, GLILD, interstitial lung disease, bronchiectasis, main antibody deficiency Main antibody deficiency (PAD) is the most common form of main immunodeficiency and consists of a group of disorders with impaired antibody production.1 Yet, even though PADs account for more than half 6-Carboxyfluorescein 6-Carboxyfluorescein of all main immunodeficiencies,2, 3 the genetic basis for the majority of PAD instances remains undefined.4 PAD continues to be under-recognized by physicians and diagnostic delays of many years 6-Carboxyfluorescein remain common.5 Delayed diagnosis can have significant consequences, including risk of severe acute infections and sequelae of inadequately controlled chronic infections. Respiratory symptoms including effective cough, wheeze, recurrent respiratory infections, and rhinosinusitus are the most common IEGF showing features of PAD.6 Notably, worsening of chronic lung disease due to structural damage from severe or chronic infections is a paramount concern for PAD individuals.7 Perhaps due to the prominent part of bacteria in lung diseases like bronchiectasis and pneumonia and the importance of antibodies in safety against bacteria, lung disease is a frequent issue for PAD individuals. In addition to bacterial infection, respiratory viruses may also lead to pulmonary exacerbations,8 yet there is a paucity of data concerning the part of viruses in bronchiectasis or other forms of chronic lung disease in PAD. Improved acknowledgement and usage of appropriate therapy in PAD individuals offers reduced the incidence of severe infections, including pneumonia, and improved survival.9, 10 However, lung disease can progress in PAD individuals despite conventional treatment with IgG replacement therapy and/or antibiotic prophylaxis.7 Importantly, interstitial lung disease (ILD) and additional pulmonary complications may not simply be the result of inadequately treated antibody deficiency or infection, but may actually be a result of immune dysfunction inherent to these individuals. OVERVIEW OF Main ANTIBODY DEFICIENCY SYNDROMES PAD consists of a diverse group of disorders resulting from fundamental problems in the ability to create effective antibody reactions against pathogens. This antibody deficiency may be due to intrinsic B cell problems, but can also involve practical impairments of additional immune cells that promote antibody reactions. As these several types of PAD each have differing examples of immunological compromise, noninfectious sequelae such as chronic lung disease, much like susceptibility to illness, varies by specific disorder. To aid in understanding the pulmonary complications that can emerge in PAD, it is helpful to briefly evaluate different etiologies of PAD generally affected by lung disease. Congenital agammaglobulinemia Congenital agammaglobulinemia results in profound absence of antibody, with designated reduction of all immunoglobulin (Ig) isotypes. This typically 6-Carboxyfluorescein results from a genetic defect impairing manifestation or signaling of the pre-B cell receptor, leading to arrest of B cell development. X-linked agammaglobulinemia (XLA) accounts for approximately 85% of individuals with congenital agammaglobulinemia and is due to mutations in the Bruton’s tyrosine kinase (BTK) gene, which is definitely carried on the X chromosome.11 Most BTK mutations result in a lack of BTK protein expression and a severe block in B cell differentiation, though there is some variability of demonstration having a genotype-phenotype correlation.12 Autosomal recessive (AR) forms of congenital agammaglobulinemia have also been described, and the block in B cell development can be more severe than in XLA.13 In.