Background Cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti‐viral cytokines and killing infected cells in the lung. Heterosubtypic T‐cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with H5N1 infection in animal challenge models. Therefore, existing T‐cell responses induced by natural infection or vaccination in humans may provide some degree of protection from infection with H5N1 strains, or may attenuate the severity of disease. Objectives To investigate heterosubtypic T‐cell responses to avian influenza in humans. Methods T‐cell responses to an overlapping set of H5 HA peptides and inactivated viruses (H1N1, H3N2 and H5N1) were assessed using IFN‐γ and IL‐2 enzyme‐linked immunospot (ELISpot) assays in a cohort of adults either vaccinated against seasonal influenza in the last 3 years (n = 20) or previously infected (n = 40). Results T‐cell responses to all three subtypes of virus were found in both infected and vaccinated individuals by IFN‐γ and IL‐2 ELISpot assays. Approximately half of the participants from each group had a positive T‐cell response to the H5 HA peptides in the IFN‐γ or IL‐2 ELISpot assay. Conclusions Heterosubtypic T‐cell responses to H5 HA occur quite frequently in vaccinated and infected individuals. Further investigation of these responses and what role they may play upon challenge or vaccination against H5N1 may assist in vaccine design for avian influenza.
Nearly 10% of children with chronic hepatitis C have anti-liver kidney microsomal (LKM)-1 antibodies. 1 LKM-1 is a marker of autoimmune hepatitis type 2, but hepatitis C virus (HCV)-positive children with a high LKM-1 antibody are regarded a separate clinical entity. 2 Bortolloti et al. compared 21 HCV-positive children with high LKM-1 antibody titre with 42 HCV-positive children with normal LKM-1 titre. All LKM-1-positive children maintained autoantibodies during follow-up without other features of autoimmunity. Immunosuppressive therapy induced prompt alanine aminotransferase (ALT) normalisation and then sustained biochemical remission in two LKM-1-positive children. In two additional patients, ALT normalised during treatment with steroids but increased again after steroids were withdrawn. 1 Clearance of HCV RNA, with normalisation of LKM antibody titre following immunosuppressive treatment in HCV RNApositive, LKM-1-positive patients has not been reported to date.We report a child with perinatal HCV who developed a significant elevation of ALT (~60 times) and associated LKM-1 antibodies (1:640) who had a biochemical resolution of hepatitis, clearance of HCV RNA from the serum with normalisation of the LKM-1 antibody titre. CaseA 19-month-old, previously well toddler, presented with perinatally acquired hepatitis C infection from her mother who had a history of intravenous drug use. Her liver function tests were normal except for an ALT of 146 (<55 IU/L). She was HCV RNA and HCV antibody positive.At 21 months, she presented with 1 week history of jaundice, mild runny nose, normal appetite but no fever, rash or other significant signs or symptoms. There was no history of travel and she had no pets. She had received amoxicillin for a sore throat 1 week earlier and one dose of paracetamol for teething related pain. She had tender hepatomegaly (3 cm below the right costal margin), splenomegaly (2-3 cm below the left costal margin), shotty cervical and inguinal lymph nodes but no stigmata of chronic liver disease.On investigation, she had a haemoglobin of 125 g/L (105-135 g/L), white cell count of 15.1 (6.0-18.0) with lymphocytosis-11 ¥ 10 9 (4-10 ¥ 10 9 ). Her direct serum bilirubin was 45 mmol/L (0-5 mmol/L), ALT 3322 IU/L (0-55 IU/L), alkaline phosphatase 423 IU/L(100-350 IU/L) and gamma glutamyl peptidase 217 IU/L (0-40 IU/L). Anti-LKM titres were 1:640 while anti-smooth muscle antibody titres were 1:40. Serology for hepatitis A, B, cytomegalovirus, Epstein-Barr virus, enterovirus, adenovirus, parvovirus B19 and human herpes virus was negative. Iron studies and celiac screen were normal. Abdominal ultrasound was normal. Because of persistent significantly elevated ALT levels over the next 12 days, 1.5 mg/kg/ day of prednisolone was commenced (Fig. 1).Liver biopsy performed 2 days later showed mild portal and lobular hepatitis suggestive of hepatitis C infection but no features of autoimmune hepatitis. As ALT improved dramatically, prednisolone was weaned by 6 weeks. HCV PCR taken at the time of commencement of st...
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