Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO

Primary Immunodeficiency Disorders (PIDs) are caused by germline variants in single genes and mostly present with recurrent or chronic infections.(1,2) The clinical presentation of PIDs is highly variable with many of them having routine infections of respiratory tract and ears due to which they may go undetected(3) . Although usual infections are common in children, an infection exceeding the expected frequency or involving multiple sites or a single, severe, unusual infection can also indicate immunodeficiency(4) . PIDs are classified into various categories by International Union of Immunological Societies (IUIS). The 2019 IUIS classification includes 430 diverse IEIs classified into categories based on the clinical and laboratory features observed in these patients(5 ).Jeffrey Modell Foundation, which is active in research, education, support and public awareness of PIDs, devised 10 warning signs of PIDs for early identification of PIDs(6,7) and includes recurrent manifestations like Sino-pulmonary infections, deep seated abscesses, failure to gain weight etc. It is estimated that around 6 to 8 million people live with PIDs worldwide, with 70% to 90% patients remaining undiagnosed(8) . High proportion of patients remaining undiagnosed can be attributed to low level of awareness among physicians, differences in diagnostic capabilities and treatment of PIDs between various regions (8,9) . In India, prevalence data of PIDs doesn’t exists, but it is estimated that more than 1 million such cases might be present(10). The Indian scenario is complicated due to lack of literature in this area, with only few centres having the clinical and laboratory experience(11,12). Although there have been advancements in the laboratory capabilities in India, there are many economical, ethical and cultural challenges that need to be addressed(10) .It is also observed that PIDs are more likely to be recognized when under 5 mortality is below 15/1000 live births, as for healthcare planners, PIDs become more relevant when deaths due to common infections gets controlled. This thus necessitates recognizing and describing such patients in the Indian scenario which has very high under 5 mortality rate and may have different clinical profile than western countries. Patients with such disorders in Asia have unique patterns of infections, especially involving organisms like Mycobacterium tuberculosis, Mycobacterium bovis, Burkholderia pseudomallei, disseminated BCGosis, etc(13) . Most of all identified PIDs are caused by defects in antibody production(8) .Patients with PID tend to have different infections by various organisms depending on the affected cell type(14,15). Complete blood count, serum immunoglobulins and flow cytometry has been used for the diagnosis of PID(15).Also, there have been many new innovations in diagnosis of PIDs including the use of Next Generation Sequencing (NGS), which not only detects specific genetic defects associated with each PID but has also led to detection of novel mutations/expanding the list of PIDs. Antimicrobial treatment, sometimes aggressive and as prophylaxis is obviously needed in some patients with PID. Patients with immunoglobulin deficiency may need intravenous (IVIG) or subcutaneous immunoglobulin (SCIG) replacement(16). Gene therapy has been used to treat patients with T cell deficiencies though the expertise and resources required is expected to limit its outreach in India. This study is therefore undertaken to add to the literature which is already in the evolving stage in the Indian scenario, as described earlier. Very few such studies are conducted, in which patients with suspected PIDs will be taken into consideration, thus providing the frequency of PIDs in suspected patients apart from describing clinical profile and etiology of such patients who get referred to the study site from varied geographic locations. Children need to be evaluated not only for primary immunodeficiency disorders, but also for other risk factors of recurrent/severe infections, especially in India where infectious disease burden predominate. This will also highlight the importance of early identification of such patients and may encourage further studies for prevention of recurrent/severe infections, as there are many such preventable risk factors.