Humoral Immunodeficiency in two patients with Alagille Syndrome

Abstract

IntroductionAlagille syndrome is an autosomal dominant entity caused by mutations that affect the Notch-Jagged1 signaling pathway. It is characterized by cholestasis due to poor bile ducts, congenital heart disease, skeletal abnormalities, ocular abnormalities and characteristic facial phenotype. We present 2 patients diagnosed with Alagille syndrome who presented associated immunodeficiency and required gammaglobulin treatment. Case 117-year-old male patient, who was liver transplanted at 19 months of the age. At 6 years of life, he underwent splenectomy secondary to immune thrombocytopenic purpura. He presented recurrent otitis and severe, large styes on the eyelids. He developed a first episode of pneumonia at 6. He received double kidney transplantation due to end-stage chronic kidney disease at 9. At the age of 10 laboratory results showed: IgG: 374 mg/dl IgM: 43 mg/dl IgE: 3 UI and IgA: 202 mg/dl. Functional responses against protein and polysaccharide antigens were absent. Lymphocytes populations were normal. He started treatment with intravenous gammaglobulin at 10 years of age. Case 27-year-old male patient with liver involvement, portal hypertension and portal vein cavernomas that evolved to hypersplenism with esophageal and gastric varices and gastrointestinal bleeding that required a splenorenal anastomosis and a stent. He presented a ventricular communication with a severe hypoplasia of the left pulmonary branch. He presented multiple infectious events including pneumococcal pneumonia. Laboratory showed pancytopenia secondary to hypersplenism, CD4 T lymphopenia (<250/uL)) with preserved CD4/CD8 ratio with normal lymphocyte proliferations, IgG: 450 mg/dl, IgM: 21 mg/dl, IgA: 136 mg/dl. A humoral response decay against global Pneumococcal capsular polysaccharide was observed. Variable response to protein antigen was present. Daily chemoprophylaxis with trimethoprim sulfamethoxazole was indicated but he repeated infectious episodes, then subcutaneous gammaglobulin was started. ConclusionsWe present2 patients diagnosed with Alagille syndromewith associated immunodeficiency. The NOTCH/Jagged 1 signaling pathway is of profound relevance to the process of somitogenesis and in the development of CD4 and CD8 lymphocytes. The immune compromise of patients with Alagille syndrome should be emphasized and eventually gammaglobulin treatment should be indicated.