Long-term survival of patients with Wegener's granulomatosis from the American College of Rheumatology Wegener's Granulomatosis Classification Criteria Cohort.

OBJECTIVE: To determine survivorship in Wegener's granulomatosis (WG) in a well-defined multicenter cohort. METHODS: Follow-up was obtained for 77 of the 85 patients enrolled in the 1990 American College of Rheumatology vasculitis classification study. RESULTS: There were 28 deaths (10 females and 18 males) among the 77 patients available for follow-up. Standardized mortality ratios (SMR) were calculated with mortality data from the general population and from this group of patients with WG (an SMR of 1 indicates that expected and observed survival are identical). Overall survivorship among patients with WG was substantially reduced in this cohort (SMR = 4.685 +/- 0.65; for females SMR = 6.814 +/- 1.571; for males SMR = 3.998 +/- 0.69). CONCLUSION: The life expectancy of patients with WG is reduced compared with the general population.

A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. The Xoma RA Investigator Group.

OBJECTIVE: To evaluate the efficacy of an anti-CD5 ricin-linked immunoconjugate (CD5-IC) in patients with rheumatoid arthritis (RA). METHODS: A total of 104 evaluable patients were enrolled in a multicenter, double-blind, multiple-dose, placebo-controlled study of CD5-IC. RESULTS: Treatment with CD5-IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5-IC, but the treatment was generally well-tolerated. CONCLUSION: At the doses used in this study, CD5-IC was ineffective for treating RA.

Long-term survival of patients with giant cell arteritis in the American College of Rheumatology giant cell arteritis classification criteria cohort.

OBJECTIVE: To characterize survivorship among patients with giant cell arteritis in a well-defined, multicenter cohort. PATIENTS AND METHODS: Follow-up was obtained for 205 (95.8%) of the 214 patients enrolled in the 1990 American College of Rheumatology vasculitis classification study. Standardized mortality ratios (SMR) were calculated comparing mortality data from this group of patients with giant cell arteritis versus the general population. RESULTS: There were 49 deaths (33 women and 16 men among the 205 patients available for follow-up. Survivorship was virtually identical to that of the general population (SMR = 1.034 +/- 0.121), and was similar for women (SMR = 1.022 +/- 0.149) and men (SMR = 1.078 +/- 0.206) (SMR = 1 indicates that expected and observed survival are identical). CONCLUSION: The life expectancy of patients with giant cell arteritis is the same as that of the general population.

Modulation of helper T cell function by prostaglandins.

OBJECTIVE: To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transformating growth factor beta 1 by CD4+ T cells. METHODS: TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E1 (PGE1) analog misoprostol and PGE2. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays. RESULTS: PGE2 and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE2 are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, TH0-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells. CONCLUSION: Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE2, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFN gamma.