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Autoimmunity after Alpha-Interferon Therapy for Malignant Carcinoid Tumors

Lars E. Rönnblom, MD, PhD; Gunnar V. Alm, MD, PhD; and Kjell E. Öberg, MD, PhD
[+] Article, Author, and Disclosure Information

Grant Support: In part by grants from the Swedish Medical Research Council and the Swedish Cancer Society.

Requests for Reprints: Kjell E. Öberg, MD, PhD: Ludwig Institute for Cancer Research, University Hospital, S-751 85 Uppsala, Sweden.

Current Author Addresses: Dr. Rönnblom: Department of Internal Medicine, Central Hospital, S-96185 Boden, Sweden.

Dr. Aim: Interferon Laboratory, BMC, Box 588, S-75123 Uppsala, Sweden.

Dr. Öberg: Ludwig Institute for Cancer Research, University Hospital, S-75185 Uppsala, Sweden.

© 1991 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1991;115(3):178-183. doi:10.7326/0003-4819-115-3-178
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Objective: To determine the incidence of autoantibodies and autoimmune disease and their influence on therapeutic results during alpha-interferon treatment in patients with malignant midgut carcinoid tumors.

Design: Consecutive sample of patients.

Setting: University hospital.

Patients: One hundred thirty-five patients (70 women, 65 men; median age, 59 years) with biopsyproven tumors, liver metastases, and no autoimmune disease.

Interventions: Leukocyte alpha-interferon (n = 88) or alpha-interferon 2b (n = 47) three times a week.

Main Outcome Measures: Signs and symptoms of autoimmune disease or development of autoantibodies to thyroid antigens, nuclear antigens, or gastric parietal cells. Tumor responses were determined by reduced liver metastases or reduced urinary 5-hydroxyindole acetic acid excretion, or both.

Results: Twenty-five patients (19%) developed the following autoimmune disorders after a median of 9 months of therapy: thyroid disease (n = 18), systemic lupus erythematosus (n = 1), pernicious anemia (n = 4), and vasculitis (n = 2). Antibodies to microsomal thyroid antigen or thyroglobulin were detected in 16 patients before therapy and in another 11 patients during therapy. Antinuclear antibodies were detected in 16 patients before and in another 19 patients during therapy. Clinical thyroid disease developed in more than 60% of patients who had or developed thyroid antibodies but in only 7% of initially autoantibody-negative patients. Autoimmunity did not correlate with objective tumor response.

Conclusion: Patients with malignant carcinoid tumors may develop autoimmune disease during alphainterferon therapy, especially when autoantibodies are present. They should therefore be monitored for autoimmunity, which does not appear, however, to influence tumor responses.





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