A CURRY,*. MN BHA1TACHARYYAt. *Public Health Laboratory Service,. Withington Hospital,. Manchester M20 8LR. tDepartment ofGenitourinary Medicine,.
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Letters to the Editor
endotoxin in the serum is found more often than in other types of viral hepatitis.2 The pyrogenic response induced by the endotoxin most probably explains why fever is a more common finding in human hepatitis A virus infection than in hepatitis B virus or hepatitis non-A, non-B virus infections.2 Moreover, the striking increase in serum IgM values, again characteristic of human hepatitis A virus infection, is not only the result of an increased production of IgM against hepatitis A virus but also reflects a non-specific increase in IgM, in Figure Faecal coronavirus from part directed against enteric bacteria.3 Consequently, a dysfunction of the Kupffer male homosexual. x 150000. cells in human hepatitis A virus infection has been postulated.2 3 Microbiological results on stool samples We had the opportunity to look for morphological evidence supporting this hypothesis. We received fresh unfixed liver Organism tissue from a patient with serologically Salmonella sp confirmed acute hepatitis A virus infection Shigella sp taken three days after the onset of jaundice. Campylobacter sp Routine histology showed portal and 0 Giardia lamblia 3 Entamoeba histolytica periportal inflammation with concomitant 2 Entamoeba coli acinar zone I necrosis. Using monoclonal 1 Endolimax nana anti-hepatitis A virus antibodies, generously 2 lodamoeba butschlii 0 donated by Dr A MacGregor Cryptosporidium 2 Small round featureless virus (Commonwealth Serum Laboratories, 8* Coronavirus Australia),4 a granular immunoreactivity 33 Total No of patients was observed in the macrophages bordering the inflammatory infiltrate and located in *Electron microscopy was performed on only 22/23 specimens. zone 1 of the parenchyma. Hepatitis A virus antigens were absent in hepatocytes. On electron microscopy, empty and full particles, as previously described in hepatitis speculative at present to suggest any 6 Kern P, Muller G, Schmitz H, et al. A virus infection,5 6 were noted in secondary Coronavirus-like particles in homosexual lysosomes of large macrophages. In spite of correlation between the finding of extensive search no such structures could be men. Klin Wochenschr 1985;63:68-72. coronaviruses in homosexuals and either identified in the surrounding liver cells. On HIV infection or AIDS. We intend to immunoelectron microscopy, however, amplify our study and to try to determine hepatitis A virus antigens were shown on the the importance of excretion of enteric T RIORDAN,* membranes of the rough endoplasmatic coronaviruses in this group of patients. A CURRY,* reticulum in some hepatocytes. MN BHA1TACHARYYAt In view of these findings we propose that *Public Health Laboratory Service, the presence of particles like hepatitis A References Withington Hospital, virus in zone 1 macrophages, resulting from Manchester M20 8LR either the phagocytic function of these cells A. I Riordan T, Craske J, Roberts JL, Curry tDepartment of Genitourinary Medicine, or from their primary infection, causes the Food borne infection by a Norwalk like Manchester Royal Infirmary, clearance dysfunction of Kupffer cells and J Clin structured round virus). virus (small Oxford Road, Pathol 1984;37:817-20. is responsible for the clinical and Manchester M13 9NL hence 2 Quinn TC, Walter E, Stamm MD, et al. The biochemical findings in human hepatitis A polymicrobial origin of intestinal infection virus infection mentioned here. in homosexual men. New Engl J Med 1983;309:576-82. 3 Tyrrell DAJ, Almeida JD, Cunningham CH, et al. Coronaviridae. Intervirology 1975; 5:76-82. 4 Caul EO, Paver WK, Clarke SKR. Coronavirus particles in faeces from patients with gastroenteritis. Lancet 1975;i: 1 192. 5 Mathan M, Mathan VI, Swaminathan SP, et al. Pleomorphic virus-like particles in human faeces. Lancet 1975;i:1068-9.
R SCIOT R DE VOS
Hepatitis A: a Kupffer cell disease?
Endotoxin values in peripheral blood and the titre of antibodies to enteric bacteria can be used as indices of Kupffer cell integrity.' In human hepatitis A virus infection
C DE WOLF-PEETERS VJ DESMET
University Hospital St Rafael, Laboratory for Histochemistry and Cytochemistry, Catholic University of Leuven, Leuven, Belgium
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Letters to the Editor References I Jones EA, Summerfield JA. Functional aspects of hepatic sinudoidal cells. Semin Liver Dis 1985;5:157-74. 2 Tanikawa K, Sata M, Setoyama H, Abe H. Changes of the Kupffer cells and clinical manifestations in acute hepatitis type A. Hepatology Rapid Literature Review 1985;15:2655. 3 Miller HFA, Legler K, Thomssen R. Increase in immunoglobulin M antibodies against gut bacteria during acute hepatitis A. Infect Immun 1983;40:542-7. 4 MacGregor A, Komitschuk M, Hurrel JGR, et al. Monoclonal antibodies against hepatitis A virus. J Clin Microbiol 1983;18:1237-43. 5 Tanaka T, Tanaka I, Koga M, et al. Morphological findings of acute hepatitis A. Acta Hepatol Jpn 1981 ;22:494-507. 6 Shimizu YK, Shikata T, Beninger PR, et al. Detection of hepatitis A antigen in human liver. Infect Immun 1982;36:320-4.
T regions. Staining for a proliferation associated antigen with the antibody Ki 673 showed that most cells within the germinal centres in PGL express this antigen. Double staining with Ki 67 and Kim 4 showed that most of these cells are DRC. In the T region numerous cells were also positive for Ki 67; their distribution and morphological features indicated that they were IDRC. Immunohistochemically Epstein Barr virus (EBV) was identified in cells of the B region, while cytomegalovirus (CMV) was present in the T and B region. In situ hybridisation detects the EBV genome in most cells of the B region, whereas most of the cells in the T region contain CMV DNA. Staining with an antibody against the gag protein p24 of HIV showed retroviral infection of some lymphocytes and several macrophages, DRC, and IDRC. Interdigitating cells showed a positive reaction in their cytoplasm, on the nuclear membrane, and within the nucleus. Characteristically these cells were these infected infected cells Characteristically, surrounded by a corona of lymphocytes whose cell membranes also stained for p24 (figure). Our results indicate that HIV or concomitant viral infections, such as EBV or CMV, or a combination, can cause a prolifrationof as well wel as DC that IDRC as as DRC proliferation of IDR have hitherto been regarded as "end cells." The detection of HIV in DRC4 and IDRC shows that the presence of the CD4 (T4) antigen is not a prerequisite for an infection by the retrovirus. The characteristic arrangement of lymphocytes staining for p24-with the reaction still restricted to the cytoplasm and sometimes found only in wer
Accessory cells as primary target of human immunodeficiency virus HIV infection We recently reported a high increase in the number of dendritic reticulum cells (DRC) that were positive for the monoclonal antibody KiM 4' in lymph nodes from patients with persistent generalised lymphadenopathy (PGL).2 Further studies on 12 PGL lymph nodes showed an increase of interdigitating reticulum cells (IDRC) positive for S100 protein and KiM 1 in the
areas in close contact with IDRC-around
infected interdigitating cells indicates that accessory cells such as IDRC, DRC, and macrophages are the first target of HIV infection and may thus serve as a reservoir for the virus. H MULLER s FALK HJ STUTTE
Department ofPathology, University ofFrankfurt, D-6000 Frankfurt 70, Federal Republic of Germany. References I Radzun JH, Parwaresch MR. Differential immunohistochemical resolution of the human mononuclear phagocyte system. Cell Immunol 1983 1982;174:83.
Stutte JH. Lymph nodes, Muller H, Falk S,and the staging of AIDS. accessory cells immunology Today 1985;6:257. 3 Gerdes J, Schwab U, Lemke H, Stein H. 2
Production of a mouse monoclonal antibody reactive with a human nuclear antigen
associated with cell proliferation. Int J Cancer 1983;31:13-20. 4 Armstrong Dawkins RL, Home R. of accessory Retroviral JA, infection and incellsAIDS. the immunological paradox
Immunological1985,6:121-2. Immunology Today 1985;6:121-2.
Figure
Diagnosis of acute myocardial infarction at T region of PGL lymph node. necropsy Interdigitating cell positive for p24 on cell membrane within We were interested to read a report of a cytoplasm and on nuclear method for diagnosing acute myocardial I
3 .A
f
membrane (centre) surrounded by T4 lymphocytes (confirmed by double staining). Their positive reaction for p24 is restricted to cell membranes indicating HIV absorption. (Cryostat section, direct immunoperoxidase.) x 1000.
damage at post mortem examination by enzyme analysis of pericardial fluid.' When death occurs within a few hours of a myocardial infarct there are often no macroscopic nor histological features to confirm the diagnosis, other than perhaps an impaired coronary arterial supply. Though techniques to show early changes have been described,2' none has proved universally acceptable, either because it is not readily available or because reproducibility is poor. A method for diagnosing acute myocardial infarction by enzyme analysis of pericardial fluid, as described' is therefore very
