RAS-associated autoimmune lymphoproliferative disorder (RALD) is a rare congenital immunodeficiency disorder caused by somatic mutations in NRAS or KRAS. Its main pathological feature is immune dysregulation-induced hematologic destruction, presenting with symptoms resembling autoimmune diseases. RALD exhibits significant clinical heterogeneity, with manifestations including autoimmune phenomena, hepatosplenomegaly, lymphadenopathy, monocytosis, and increased susceptibility to infections. Owing to its rarity and its unclear nature, a standardized therapeutic regimen for RALD is currently lacking. This review summarizes the latest advances in the pathogenesis, clinical manifestations, differential diagnosis, and treatment of RALD, aiming to provide new insights and reference for the understanding and management of this disorder.
Humans ; Lymphoproliferative Disorders/etiology* ; Autoimmune Diseases/etiology* ; Autoimmune Lymphoproliferative Syndrome/genetics* ; GTP Phosphohydrolases/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Mutation ; Membrane Proteins

OBJECTIVETo summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) .

METHODThe patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed.

RESULTThe patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 10⁹/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαβ⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available.

CONCLUSIONALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.

Autoimmune Lymphoproliferative Syndrome ; diagnosis ; therapy ; Cell Count ; Humans ; Infant ; Male ; T-Lymphocyte Subsets ; Vitamin B 12 ; blood ; fas Receptor

Autoimmune Lymphoproliferative Syndrome ; diagnosis ; genetics ; immunology ; therapy ; Biomarkers ; blood ; Child, Preschool ; Humans ; Male ; Mutation ; Prednisolone ; administration & dosage ; therapeutic use ; Ultrasonography, Doppler, Color ; fas Receptor ; genetics

Autoimmune Lymphoproliferative Syndrome ; Humans

Sjogren's syndrome is a systemic autoimmune disease characterized by sicca symptoms and B lymphocyte hyperactivity. Hematological abnormalities are common in Sjogren's syndrome, including anemia, leukopenia, thrombocytopenia, and lymphoproliferative disorders. These hematologic involvements are mostly recognized as mild laboratory abnormalities. Life-threatening, severe thrombocytopenia is very rare. We describe a patient with primary Sjogren's syndrome, who developed very severe thrombocytopenia during the clinical course and successfully treated with high dose dexamethasone therapy.
Anemia ; Autoimmune Diseases ; Dexamethasone ; Humans ; Leukopenia ; Lymphocytes ; Lymphoproliferative Disorders ; Purpura ; Sjogren's Syndrome ; Thrombocytopenia

Autoimmune Lymphoproliferative Syndrome ; classification ; diagnosis ; immunology ; physiopathology ; therapy ; Child, Preschool ; Diagnosis, Differential ; Disease Progression ; Humans ; Infant ; Treatment Outcome

Animals ; Apoptosis ; genetics ; immunology ; Apoptosis Regulatory Proteins ; genetics ; Autoimmune Lymphoproliferative Syndrome ; genetics ; immunology ; physiopathology ; Humans ; Mutation ; T-Lymphocytes ; immunology