Study of pattern of Primary Immunodeficiency (PID) in Western India with a view to establish a diagnostic algorithm suitable for this population. :
a. Established facilities for diagnosis of Primary Immunodeficiency disorders (PID). More than 2000 cases were investigated for PID and 273 cases of distinct PIDs were diagnosed.
b. Established facilities for molecular characterization of common PIDs like LAD-I, X-HIGM, ALPS, CGD, FHL2, MSMD and SCID.
c. Established facilities for second trimester prenatal diagnosis for some severe forms of PID. Prenatal diagnosis was performed for total 29 couples at risk by flowcytometry including one case of XLA, four cases of LAD-I, seven cases of SCID and three case of CGD and three couples with FHL2 by molecular techniques. Prenatal diagnosis by CVS and molecular techniques was performed in cases of LAD-I and cases of FHL2 (perforin deficiency)
d. Established diagnostic algorithms for diagnosis of individual PIDs including SCID, antibody deficiencies and CGD.
Development of a rapid granule release assay for evaluation of genetic Hemophagocytic Lymphohistiocytosis (HLH). :
Developed a rapid assay based on whole blood flow cytometry technique for diagnosis of genetic HLH and validated in diagnosing various forms of FHL (familial HLH) patients.
Understanding Molecular pathology of Hemophagocytic Lymphohistiocytois (HLH) in India :
a. Total 119 patients fitting into HLH criteria of Histiocyte society, 42 (35%) FLH patients were evaluated under this project.
b. Of total 18 patients with Perforin Deficiency molecular characterization was completed in 10 patients. Two nonsense mutations (p.Gln164X and p.Cys176X), both novel, and eight missense mutations including four novel mutations (p.Ala278Asp, p.Asp340Asn, p.Cys395Arg and p.Ala415Thr) and four known missense mutation (p.Gly220Arg, p.Try129Ser, p.Arg177Ser and p.Asp491Asn) were identified in these patients.
Immunological and Molecular Characterization of patients with Hyper immunoglobulin M (HIGM) Syndrome :
a. Patients with suspected antibody deficiency were evaluated for HIGM. Total 9 patients were diagnosed with HIGM, 8 were X-linked HIGM with CD40L deficiency and one was autosomal recessive HIGM with CD40 deficiency.
b. Mutations in 7 out of 8 cases of X-HIGM have been characterized of which 5 cases showed novel mutations and one case showed a reported mutation
Study of Biology of Leukemic Stem Cells :
a. Under this project immunophenotypic characterization of normal haematopoietic stem cells and leukemic stem cells is standardized.
b. Protocols for 4 important signaling molecules has been standardized in normal hematopoietic cells and is tested on 20 leukemic stem cells
Age Related Blood Lymphocyte Subsets in Healthy Indian Children – A Multicentric Study :
a. Under this multicentric task force project we are establishing normal ranges of different lymphocyte subsets at different paediatric population from birth to 18 years of age.