Interferon‐γ and urine neopterin in attacks of the hyperimmunoglobulinaemia D and periodic fever syndrome

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Abstract
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 lesions and a polyclonal elevation of serum IgD (> 100 Umr-1). Interferon-gamma (IFN-γ) is a major proinflammatory cytokine which could play a role in the pathogenesis of the attacks. There is a need for parameters (if possible non-invasive) to monitor disease activity. A potential candidate is neopterin which is released by monocytes/macrophages when stimulated with IFN-γ, excreted unchanged in urine, and appears to be an early and sensitive marker for activation of the immune system. We measured rectal body temperature, serum IFN-γ, and urine neopterin in 10 hyper-IgD patients both during and between attacks. The body temperature rose to a mean of 38–9d̀C on the first day of the attack and normalized within 5 days. Serum IFN-γ during the first day of the attack was 2.98 IUmL-1 and was significantly lower during remissions. The urine neopterin excretion was 268 ± 170 μmolmol-1 creatinine between attacks and was significantly increased to 638 ± 275 μmolmor-1 creatinine on the first day of symptoms. Maximal urine neopterin values were reached on the fourth day of the attack (1051 ± 387 μmolmor-1 creatinine) and excretion gradually declined and attained values below 400 μmolmol- ' creatinine after 9 days. There was a good correlation between serum IFN-γ and urine neopterin. The increases in serum IFN-γ and urine neopterin suggest activation of the cellular immunity during the febrile attacks of the hyper-IgD syndrome. Furthermore, the activation of the cellular immune system appears to persist several days after normalization of the body temperature. The significant correlation between IFN-γ; and urine neopterin in the hyper-IgD syndrome accords with experimental data suggesting that IFN-γ is the dominant factor in the release of neopterin. Our study shows that urinary neopterin is a good quantitative and qualitative parameter to monitor disease activity in patients with the hyper-IgD syndrome