Intravenous immunoglobulin treatment of congenital parvovirus B19 induced anemia - a case report.

BACKGROUND: Parvovirus is a common childhood infection that could be very dangerous to the fetus, if pregnant women become infected. The spectrum of effects range from pure red blood cell aplasia with hydrops fetalis to meningoencephalitis, with many symptoms in between. Severe anemia in the setting of pure red blood cell aplasia is one of the more common effects that neonatal experience (if infected intrapartum), with the current gold standard treatment being intrauterine or postnatal packed red blood cell (PRBC) transfusions, yet intravenous immunoglobulin (IVIG) may be a superior treatment option. CASE PRESENTATION: A preterm infant was born at 26th week of gestational age via emergency Cesarean section due to hydrops fetalis, with parvovirus B19 exposure one month prior. The infant tested positive for IgM antibodies against parvovirus B19. Among many other serious complications of both hydrops fetalis and premature delivery, the infant had severe unremitting anemia, and received many PRBC transfusion over the course of his 71-day-long neonatal intensive care unit stay. During a follow up appointments as outpatient, his blood tests showed persistent high copies of parvovirus B19. He was then supported with PRBC transfusions and treated with IVIG. After three doses of IVIG, the infant's parvovirus B19 viral copy numbers have dramatically reduced and the infant did not require any more PRBC transfusions. CONCLUSIONS: IVIG infusion effectively treated the parvovirus B19 infection and restored erythropoiesis making the child transfusion independent. Furthermore, since IVIG is safe and readily crosses the placenta, further studies are needed to determine if IVIG should be considered as an alternative prenatal treatment for congenital parvovirus B19 infection.

Bortezomib induces nuclear translocation of IκBα resulting in gene-specific suppression of NF-κB--dependent transcription and induction of apoptosis in CTCL.

Cutaneous T-cell lymphoma (CTCL) is characterized by constitutive activation of nuclear factor κB (NF-κB), which plays a crucial role in the survival of CTCL cells and their resistance to apoptosis. NF-κB activity in CTCL is inhibited by the proteasome inhibitor bortezomib; however, the mechanisms remained unknown. In this study, we investigated mechanisms by which bortezomib suppresses NF-κB activity in CTCL Hut-78 cells. We demonstrate that bortezomib and MG132 suppress NF-κB activity in Hut-78 cells by a novel mechanism that consists of inducing nuclear translocation and accumulation of IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), which then associates with NF-κB p65 and p50 in the nucleus and inhibits NF-κB DNA binding activity. Surprisingly, however, while expression of NF-κB-dependent antiapoptotic genes cIAP1 and cIAP2 is inhibited by bortezomib, expression of Bcl-2 is not suppressed. Chromatin immunoprecipitation indicated that cIAP1 and cIAP2 promoters are occupied by NF-κB p65/50 heterodimers, whereas Bcl-2 promoter is occupied predominantly by p50/50 homodimers. Collectively, our data reveal a novel mechanism of bortezomib function in CTCL and suggest that the inhibition of NF-κB-dependent gene expression by bortezomib is gene specific and depends on the subunit composition of NF-κB dimers recruited to NF-κB-responsive promoters.

Inhibition of adjuvant-induced arthritis by systemic tissue inhibitor of metalloproteinases 4 gene delivery.

OBJECTIVE: An imbalance in the matrix metalloproteinase:tissue inhibitor of metalloproteinases (MMP:TIMP) ratio in favor of MMP appears to be an important determinant of tissue damage in arthritis. We undertook this study to explore whether reversal of this imbalance in favor of TIMP would alter this process and to examine the mechanism of this alteration. METHODS: We administered human TIMP-4 by electroporation-mediated intramuscular injection of naked DNA using the rat adjuvant-induced arthritis (AIA) model. RESULTS: Intramuscular naked TIMP-4 gene administration resulted in high circulating TIMP-4 levels and completely abolished arthritis development in the rat AIA model. This inhibition was associated with significantly decreased MMP activity in the joint tissue as well as with significantly decreased serum and tissue tumor necrosis factor alpha levels and serum interleukin-1alpha levels compared with animals with arthritis. The mutation of cysteine at position 1 of TIMP-4 failed to block the development of AIA. CONCLUSION: Our data indicate that TIMP-4 is a potent antiinflammatory agent, and that its antiarthritis function may be mediated by MMPs. Arthritis-inhibiting effects of TIMP-4 may suggest a unique application of this gene therapy method for arthritis.