Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
A Mechanism to Explain the T lymphopenia
- Trevor G Marshall, Frances E. Marshall (20 June 2003)
-
Lymphopenia in SARS - Apoptosis?
- D. Roddy O'Donnell, Robert C. Tasker, and Michael F.E. Roe (24 June 2003)
-
PCR and GM-ELISA diagnosis of aspergillosis for SARS patients received corticosteroids treatment
- Ya Ping Wu, Ran. Wei,(Basic Medical Science Institute, Taishan Medical College, Taian, Shandong, China 271000)Jan. Verhoef, (Eijkman-Winkler Centre for Medical Microbiology, Infectious Diseases and Inflammation,University Medical Center Utrecht,,the Netherlands, (3 October 2003)
|
|
|||
|
Trevor G Marshall, Managing Editor, JOIMR.org Thousand Oaks, California 91360, Frances E. Marshall
Send response to journal:
|
SARS patients frequently die from the same Th1 cytokine cascade which also kills (albeit much more slowly) sarcoidosis patients. It might be expected that a Th1 cytokine cascade would be associated with high levels of T-lymphocytes, yet the opposite is true, advanced cases of sarcoid inflammation often present with T lymphopenia. In sarcoidosis this is especially true while the inflammation is progressing to an advanced stage, or while inflammation is exacerbated by the Jarisch-Herxheimer Shock which occurs during anti-microbial therapy. This correlates with the study's observation that a similar exacerbation of T lymphopenia correlated with poor prognosis in SARS. We have postulated a mechanism to explain that behaviour. The SARS pathogen is a virus. Lee has published an analysis of the SARS Coronavirus genome at JOIMR [1] where he proposes that the SARS coronavirus is able to mimic the "T-lymphocyte Receptor alpha-beta V protein" due to "a superantigen between residues 690 through 1050 of the SARS E2-spike protein". If this was indeed the case, then any SARS coronavirus which was living within the immune system's monocytes and macrophages would cause them to be self-activating, and they would not need an activated T-lymphocyte to trigger the continuing release of the catastrophic cytokine cascade. The immune system would run out-of-control. The lymphopenia could then result from a down-regulation of lymphocyte differentiation. This hypothesis would also explain why the virus is sometimes hard to detect in the bloodstream. 1. Lee RE: SARS E2-spike Protein Contains a Superantigen Between Residues 690 through 1050. JOIMR 2003;1(1):3 [Publisher Full Text] 2. Marshall TG: A Potential Blood Test for SARS Triage. [Rapid Response] BMJ, 5 May 2003. [Full Text] Competing interests: None declared |
|||
|
|
|||
|
D. Roddy O'Donnell, Associate Lecturer Paediatrics, Clinical School, University of Cambridge, CB2 2QQ, UK, Robert C. Tasker, and Michael F.E. Roe
Send response to journal:
|
Sir—The recent clinical reviews of the severe acute respiratory syndrome (SARS), including the recent article by Wong et al. 1 in this week’s BMJ have commented on the presence of pronounced lymphopenia in patients. It has been described as one of the hall mark laboratory features. Panesar has suggested the use of glucocorticoids or stimulation of the hypothalamic-pituitary-adrenal axis leading to T lymphocytes being driven out of the peripheral circulation and suggests that patients without lymphopenia may in fact be adrenal insufficient2. We would like to draw attention to apoptosis, a recently described mechanism of lymphopenia that we feel is more likely to be important and needs further investigation. It has been noted that in severe paramyxovirus infections in humans such as measles, lymphopenia is commonly present and associated with worse disease. We have recently reported that the same phenomenon is also seen with another paramyxovirus infection: respiratory syncytial virus (RSV) which causes bronchiolitis in young children3. Children with more severe RSV bronchiolitis were shown to have significantly lower absolute lymphocyte counts compared with those with mild disease and a measurable neutrophilia. Bronchiolitis is a ubiquitous illness and in the developed world, the commonest reason a child under one year of age is admitted to hospital. Interestingly, from studies in mice it is clear that although the immune response to virus is essential in controlling the virus it may also be responsible for the illness4. The fact the immune response is both saint and sinner is believed to be why the use of Ribavirin has proved less effective in bronchiolitis than was first hoped. There are clear parallels between these severe viral illnesses and models of sepsis where lymphopenia is also present. In both sepsis and measles infection bystander programmed cell death, apoptosis, is believed to be the mechanism by which lymphopenia occurs. In the mouse model of sepsis it is clear that inhibitors of apoptosis may ameliorate illness and prevent death5. There may be important therapeutic implications for patients with SARS from these new and exciting research areas. References 1. Wong RS, Wu A, To KF, Lee N, Lam CW, Wong CK et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003;326:1358-62. 2. Panesar NS. Lymphopenia in SARS. Lancet 2003;361:1985. 3. O'Donnell DR,.Carrington D. Peripheral blood lymphopenia and neutrophilia in children with severe respiratory syncytial virus disease. Pediatr.Pulmonol. 2002;34:128-30. 4. Openshaw PJ. Immunopathological mechanisms in respiratory syncytial virus disease. Springer Semin.Immunopathol. 1995;17:187-201. 5. Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat.Immunol. 2000;1:496-501. Competing interests: None declared |
|||
|
|
|||
|
Ya Ping Wu, researcher Dept. Haematology, University Medical Center Utrecht, 3584CX Utrecht, the Netherlands,, Ran. Wei,(Basic Medical Science Institute, Taishan Medical College, Taian, Shandong, China 271000)Jan. Verhoef, (Eijkman-Winkler Centre for Medical Microbiology, Infectious Diseases and Inflammation,University Medical Center Utrecht,,the Netherlands,
Send response to journal:
|
TO THE EDITOR: Currently there is no consensus and or FDA approved treatment for SARS. In June 21 issue, Dr. Raymond S M Wong reported that for all SARS patients received broad spectrum antibiotics and a combination of ribavirin and prednisolone 0.5 mg/kg/day as empirical treatment. Intravenous methylprednisolone at high dosage was used in patients with respiratory distress or progressive consolidations on their chest radiograph. (1) But the treatment of SARS patients with ribavarin and corticosteroids remains controversial.(2) The underlying idea of administering corticosteroids is the possible suppression of the cytokine storm that may worsen lung injury caused by the infectious agent. (2) And the sceptical idea is use of corticosteroids with possibly ineffective antiviral agents in patients with viral-induced pneumonitis can be hazardous.(2) We believe, if one decide to administer corticosteroids, one should be aware of complications such as superinfections with Aspergillus,(3) which is a known complication in any patient receiving corticosteroids (4). Therefore we suggest to monitor SARS patients receiving corticosteroids for aspergillosis. Since cultures for Aspergillus are usually very slow (it may take up to six days) and characterized by low sensitivity, we would advice to introduce a real time polymerase chain reaction (PCR) assay for the detection of 18SrRNA Aspergillus-specific sequences with bronchoalveolar lavage (BAL) fluid specimen, especially when used in association with galactomannan (GM) antigen detection by Enzyme-Linked Immunosorbent Assay (ELISA) as is recently described by Sanguinetti et al (5). This promising method for diagnosis of aspergillosis is a highly sensitive, fast and specific noninvasive procedure, it is certainly less traumatic than lung biopsy. (5, 4) However, we also feel that clinical presentation, radiology and direct microbiological examination from culture for bacteria and fungi remains essential. These assays may lead to early detection and possible to a very early treatment of Aspergillus, which is mandatory in any patient suspected of aspergillosis. It could be argued that if any of the four tests mentioned is positive for Aspergillus treatment should be instituted. In conclusion, when SARS patients are given costicosteroids, patients should be continuously monitored for possible superinfections. Cultures together with real time PCR and galactomannan (GM) or other antigen, antibody ELISA are important diagnostic features in order to make early treatment of asperagillus possible. References 1. Wong RS, Wu A, To KF, Lee N, Lam CW, Wong CK, Chan PK, Ng MH, Yu LM, Hui DS, Tam JS, Cheng G, Sung JJ. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ. 2003;326(7403):1358-62. 2. Oba, Y. Lee N., Sung JJ. The Use of Corticosteroids in SARS. Correspondence and the authors reply, N Engl J Med 2003;348(20):2034-2035. 3. Wang H, Ding Y, Li X, et al. Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. N Engl J Med 2003;349(5):507-508. 4. Muller FM, Trusen A, Weig M. Clinical manifestations and diagnosis of invasive aspergillosis in immunocompromised children. Eur J Pediatr. 2002;161(11):563-74. 5. Sanguinetti M, Posteraro B, Pagano L, Pagliari G, Fianchi L, Mele L, La Sorda M, Franco A, Fadda G. Comparison of real-time PCR, conventional PCR, and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis. J Clin Microbiol. 2003 Aug;41(8):3922-5. Competing interests: None declared |
|||