Assessment of the Rate of Decrease in Serum IgG4 Level of Autoimmune Pancreatitis Patients in Response to Initial Steroid Therapy as a Predictor of Subsequent Relapse.

OBJECTIVES: Autoimmune pancreatitis (AIP) responds well to steroid therapy but frequently relapses after discontinuing the steroid. It is difficult to know which cases are most likely to relapse. The aim of this study was to investigate the relation between the rate of decrease in serum IgG4 level after initial steroid therapy and a relapse. METHODS: The subjects were 47 AIP patients who received steroid therapy. We calculated the difference between their serum IgG4 levels before and 2 months after the start of therapy, and their rate of decrease in serum IgG4 level after treatment (Δ') by dividing the difference between the 2 values by the number of days between them. RESULTS: The rates of decrease were significantly higher in the nonrelapse groups than in the relapse groups. A receiver operating characteristic curve showed that the area under the curve for the Δ' value was 0.781, and that at the Δ' cutoff value of 10.7, the sensitivity and the specificity of the Δ' value for discriminating between the 2 groups were 0.846 and 0.632, respectively. CONCLUSIONS: Our data suggest that the rate of decrease in serum IgG4 level may be a useful predictor of a relapse of AIP after steroid therapy.

Reduced expression of an RNA-binding protein by prolactin leads to translational silencing of programmed cell death protein 4 and apoptosis in newt spermatogonia.

Recent studies indicate that the balance between cell survival and proapoptotic signals determines which cells commit to life or death. We have shown that the balance between follicle-stimulating hormone and prolactin determines differentiation or apoptosis in 7th generation spermatogonia during newt spermatogenesis; however, the molecular mechanisms specifying their fate are poorly understood. Here we show that the newt RNA-binding protein (nRBP) plays a critical role in determining their fate. nRBP was identified as a clone whose mRNA is decreased by prolactin, resulting in the reduction of the protein, which is otherwise expressed predominantly in the spermatogonia. nRBP protein associated with the mRNA for newt programmed cell death protein 4 (nPdcd4) at the 3'-untranslated region. nRBP reduction increased nPdcd4 mRNA but decreased its protein. In a cell-free system, cytoplasmic extracts containing reduced amounts of nRBP and nPdcd4 protein induced apoptosis, whereas adding nRBP protein to the extracts blocked apoptosis. Furthermore, overexpression of nRBP protected cells from apoptosis, stabilized the chimeric transcript containing the nPdcd4 3'-untranslated region, and accelerated its translation. These data suggest that, in the absence of nRBP, nPdcd4 mRNA is not stabilized and its translation is suppressed, leading to apoptosis in the spermatogonia.