Anti-cytoplasmic Autoantibodies in Hodgkin's Lymphoma

A 42-year old male patient with anamnesis of bronchial asthma presented himself with exertional dyspnea. High titer antibodies of cytoplasmic pattern in the indirect immunofluorescence test (IIFT) on HEp-2cells, not attributable to common specificities like anti-tRNA-synthetases, anti-signal recognition particle (SRP) or anti-ribosomal proteins (RPs) prompted the molecular biological approach for determination of antigen specificity. In-depth investigation of the patient's clinical settings revealed a lymphocyte predominant Hodgkin's lymphoma, which could be brought to complete remission by chemotherapy.

Immunoprecipitation of 35S-methionine labelled cell proteins, cDNA-library screening, sequencing of clones reactive with the patient serum, and expression of recombinant candidate proteins in E. coli, their purification, and western blotting were performed to verify and confirm the antibody specificities.

The patient's autoantibodies reacted with the three insulin-growth-factor-2-RNA binding proteins (IGF2BP1-3) and a rare centromere protein (CNP27). The antibody titer determined by IIFT declined from initially 1:3000 to 1:800 five years after successful therapy of the Hodgkin's lymphoma.

Anti-cytoplasmic antibodies, detectable by conventional IIFT, mainly belonging to the category of anti-tRNA-synthetases (e.g. anti-Jo1), SRP or RPs are in the first instance suspicious for systemic autoimmune rheumatic diseases (myopathies, interstitial lung disease). Their association with Hodgkin's lymphoma has been described only once in association with anti-Jo 1-syndrome [1]. The existence of anti-cytoplasmic antibodies of different specificities, demonstrated in this patient, may alert the laboratory's attention to provide the clinician with diagnostically relevant information beyond the perspective of systemic autoimmune rheumatic diseases.