INTERFERON-GAMMA AND URINE NEOPTERIN IN ATTACKS OF THE HYPERIMMUNOGLOBULINEMIA-D AND PERIODIC FEVER SYNDROME

The hyperimmunoglobulinaemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent unpredictable febrile attacks with abdominal pain, joint involvement (arthralgias/arthritis), headache, skin lesio ns and a polyclonal elevation of serum IgD(>100 U mL(-1)). Interferon- gamma (IFN-gamma) is a major proinflammatory cytokine which could play a role in the pathogenesis of the attacks. There is a need for parame ters (if possible non-invasive) to monitor disease activity. A potenti al candidate is neopterin which is released by monocytes/macrophages w hen stimulated with IFN-gamma, excreted unchanged in urine, and appear s to be an early and sensitive marker for activation of the immune sys tem. We measured rectal body temperature, serum IFN-gamma, and urine n eopterin in 10 hyper-IgD patients both during and between attacks. The body temperature rose to a mean of 38.9 degrees C on the first day of the attack and normalized within 5 days. Serum IFN-gamma during the f irst day of the attack was 2.98 IU mL(-1) and was significantly lower during remissions. The urine neopterin excretion was 268 +/- 170 mu mo l mol(-1) creatinine between attacks and was significantly increased t o 638 +/- 275 mu mol mol(-1) creatinine on the first day of symptoms. Maximal urine neopterin values were reached on the fourth day of the a ttack (1051 +/- 387 mu mol mol(-1) creatinine) and excretion gradually declined and attained values below 400 mu mol mol(-1) creatinine afte r 9 days. There was a good correlation between serum IFN-gamma and uri ne neopterin. The increases in serum IFN-gamma and urine neopterin sug gest activation of the cellular immunity during the febrile attacks of the hyper-IgD syndrome. Furthermore, the activation of the cellular i mmune system appears to persist several days after normalization of th e body temperature. The significant correlation between IFN-gamma and urine neopterin in the hyper-IgD syndrome accords with experimental da ta suggesting that IFN-gamma is the dominant factor in the release of neopterin. Our study shows that urinary neopterin is a good quantitati ve and qualitative parameter to monitor disease activity in patients w ith the hyper-IgD syndrome