Anti-CD20 monoclonal antibody for the treatment of refractory autoimmune haemolytic anaemia associated with idiopathic membranous nephropathy

Sir, We report here the efficiency of anti-CD20 monoclonal antibody in two immune-mediated diseases occurring in a 46-yr-old man. The patient suffered from a corticoresistant autoimmune haemolytic anaemia associated with an idiopathic membranous nephropathy. He made a complete recovery with anti-CD20 monoclonal antibody (rituximab) infusions. Such a case has not been previously reported to our knowledge, and confirms the role of anti-CD20 monoclonal antibody in treatment of autoimmune disorders by the way of a B-cell depletion. A 46-yr-old man was admitted to our department in January 2003, with a 3-month history of fatigue, mild pre-tibial oedema and dyspnoea. He had no medical history. Physical examination at admission was unremarkable, with the exception of pallor and mild jaundice. Full blood count at admission showed a normochromic and macrocytic anaemia (haemoglobin = 5.6 g/dl) with reticulocytosis (absolute reticulocyte count = 135 × 109/l) and normal white blood cell and platelet counts. Total and unconjugated bilirubin levels were increased (1.35 mg/dl and 1.02 mg/dl, respectively) as well as lactate dehydrogenase levels (2345 U/l; normal <600); serum haptoglobin level was undetectable. The direct Coombs test was positive and binding of IgG to the red blood cell surface was observed using anti-human globulin monospecific antibodies. Bone marrow aspirate and biopsy demonstrated normal representation of myeloid and megakaryocyte precursors, and high erythroblastic hyperplasia due to peripheral haemolysis. A nephrotic syndrome with hypoproteinaemia (49 g/l), hypoalbuminaemia (23 g/l) and a high level of urinary albumin (14 g/24 h). Cytobacteriological urinary tests were normal and no Bence-Jones protein was detected. Serum electrophoresis yielded no monoclonal gammopathy, and serum immunoglobulins were diminished for IgG (3.1 g/l, 6.9<normal range<14.0), whereas IgM and IgA were within the normal range. The following blood tests were within the normal range or negative: creatinine clearance, urea and electrolytes, glucose, cholesterol, triglycerides, thyroid function, liver function, creatine kinase, coagulation screening, vitamin B12, red cell folate, cryoglobulins, complement fractions C3/C4/CH50, antinuclear antibodies, anti-DNA and anti-SSA, anti-SSB, anti-RNP, anti-Sm anti-neutrophil cytoplasmic antibodies, peripheral lymphocyte immunophenotyping, serological tests for parvovirus B19, hepatitis B and C, human cytomegalovirus, HIV and Epstein–Barr virus, prostatic specific antigen and carcino-embryonic antigen. Moreover, a search for a hereditary haemolytic anaemia was negative (G6PD, pyruvate kinase, haemoglobin electrophoresis). Chest X-ray, body scan and digestive endoscopies were normal. Renal histology performed 2 weeks after admission showed stage I membranous glomerulonephritis.