Infections are cytokines with both antiviral and antiproliferative properties. IFN-a increases the expression of human lymphocyte antigen (HLA) class I and II, which results in a magnified activity of both helper and cytotoxic lymphocytes, and subsequent upregulation of the immune system. This, in turn, can lead to the induction of a new autoimmune disease, or to the exacerbation of an existing autoimmune disease. Shortly after IFN-a2b was Food and Drug Administration-approved for the therapy of hepatitis C, came reports that showed a worsening of amino-transferase levels in HCV patients during therapy, with an autoimmune
Serological ANA positivity Anticardiolipins antibodies Antithyroid antibodies Antismooth muscles antibodies Rheumatic factor Cryoglobulins-related Vasculitis Neuropathy Lymphoproliferative diseases Monoclonal gammopathy Low-grade lymphoma Musculoskeletal manifestations Polyarthralgia RA SLE
Glandular manifestations Thyroiditis Sialoadenitis Sjogren's syndrome Autoimmune liver disease
Autoimmune hepatitis Antiphospholipid syndrome and thrombotic disorders Renal manifestation Membranoproliferative GN Membranous GN Acute proliferative GN
hepatitis-like picture (24-27). Over the past 10 yr, numerous reports have described de novo autoimmune conditions that appeared to be hastened by IFN therapy (Table 2). Most of these manifestations appear to improve after the cessation of interferon (IFN).
Okanoue et al. (28) studied the IFN-related autoimmune complications of677 patients with chronic HCV who underwent antiviral therapy. These conditions included autoimmune thyroiditis (18 patients); hemolytic anemia (two patients); rheumatoid arthritis (RA) (two patients); immune-mediated thrombocytopenia (ITP), psoriasis, and systemic lupus erythematosus (SLE)-like syndrome (one patient each). In that retrospective study, the autoimmune complications generally occurred from 12 to 20 wk after starting IFN. After cessation of therapy, most of these entities completely resolved.
Table 2 Autoimmune Effects of IFN in Chronic Viral Hepatitis Patients
Endocrine Thyroid autoantibodies Graves' disease
De novo insulin-dependent diabetes mellitus Dermatologic Alopecia Vitiligo Hematologic Hemolytic anemia Autoimmune thrombocytopenia Factor VIII inhibitors Rheumatologic ANA positivity Systemic lupus-like syndrome Immune-complex vasculitis Renal Membranous GN Nephrotic syndrome Pulmonary De novo sarcoidosis Interstitial pneumonitis Neuromuscular
Peripheral neuropathy Myelopathy Gastrointestinal and Hepatic De novo biliary cirrhosis De novo celiac disease Ischemic colitis
Data adapted from refs. 76-79.
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