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At least 37 records · Page 2Linked to original sources
PubMed1981

The significance of abnormal immune responses in patients with multiple sclerosis.

Early diagnosis of multiple sclerosis (MS) may be assisted by tests for the abnormal immune responses of the central nervous system (CNS) including oligoclonal IgG bands in the cerebrospinal fluid (CSF), increased CNS IgG synthesis, increased CNS antibody synthesis against multiple viruses and increased numbers of enlarged lymphoid cells in the CSF. Alterations in immunological responses are important in the pathogenesis of MS. Further studies are needed, however, to identify the antigen(s) and/or antibodies responsible for oligoclonal IgG in the CSF of MS patients. Also, the cause(s) for the other immunological abnormalities with diagnostic importance need to be identified. The increased synthesis of antibodies against multiple unrelated viruses suggests generalized alteration in the immune regulatory system. The etiology of MS might be multifactorial involving abnormal immunological responses, possibly precipitated by infectious agents acquired during childhood by genetically susceptible individuals. The immunological responses including alterations in myelin basic protein concentration, antimyelin antibody and immune complex activities in CSF, and in vitro stimulation, suppression and migration inhibition of blood lymphocytes appear to correlate with stage of MS and severity of CNS damage. Some of the tests may become useful in estimating the prognosis of the disease. Longitudinal studies are needed to clarify the sensitivity of the diagnostic and prognostic immunological tests and etiological significance of these abnormalities in MS.

Antibodies, Viral↗
PubMed2000

The use of standardized extracts in allergen immunotherapy.

BACKGROUND: Double-blind, placebo-controlled studies have established that injection allergen immunotherapy is clinically effective. However, it is not known to what extent the doses of allergen extract commonly used in clinical practice match those that have been used in these controlled studies. OBJECTIVE: The aim of this study was to determine by questionnaire the doses of standardized allergen extracts commonly used by board-certified allergists in the United States and to compare these with doses that have proven effective in double-blind, placebo-controlled studies. METHODS: A questionnaire containing a hypothetical case and asking for a recommended allergen prescription for maintenance immunotherapy was mailed to 500 randomly selected board-certified members of the American Academy of Allergy, Asthma and Immunology living in the United States. The recommended doses were compared with those doses of the extracts that had been proven effective by using major allergen content figures for representative standardized US allergen extracts provided by an allergy extract laboratory. RESULTS: Responses were received from 118 (23%) of the addressees. Eighty (16%) contained interpretable data on maintenance dosing for extracts. The median doses of pollen recommended were comparable with those that have been demonstrated to be clinically effective. Median doses of house dust mites were only slightly lower than those that have proven effective. Median doses of animal dander, on the other hand, were well below those used effectively in controlled studies. Although the median doses used were often in the range of proven doses, the range of doses recommended by allergists included some that were one tenth to one five hundredth those of the median doses. CONCLUSION: In the absence of useful guidance from the federal regulatory authorities, American allergists, for the most part, use doses of pollens and house dust mites that are within the proven range. Their dosing of animal dander is generally below proven effective doses. There is, however, a wide range of dosing of all extracts used, and there is use of mixes that have no botanical basis. Therefore there is need for studies defining what are effective and ineffective allergen extract doses.

Allergens↗
PubMed2001

Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: a possible role for mast cells in late-phase allergic reactions.

BACKGROUND: Mast cells and eosinophils are believed to interact during the late and the chronic stages of allergic inflammation. OBJECTIVE: In this study we investigated whether eosinophils can cause activation and consequent histamine release of already challenged mast cells, a situation likely to take place during the allergic late-phase reaction. METHODS: Rat peritoneal mast cells presensitized with IgE anti-dinitrophenol-human serum albumin and challenged by dinitrophenol-human serum albumin or compound 48/80 were incubated with either eosinophil sonicate or major basic protein (MBP). Eosinophils were purified from the peripheral (>98%) blood of mildly allergic patients. Heparin and pertussis toxin and different extracellular Ca(2+) concentrations were used to modulate mast cell reactivation by MBP. Histamine release was assessed as a marker of mast cell activation. RESULTS: IgE-challenged mast cells were sensitive to reactivation induced by eosinophil sonicate and MBP. Reactivation was not cytotoxic for the mast cells. Mast cells previously challenged with compound 48/80 did not respond to subsequent MBP activation. Furthermore, heparin and pertussis toxin both inhibited mast cell reactivation induced by MBP. The ability of eosinophil sonicate and MBP to activate mast cells was not significantly affected at the different Ca(2+) concentrations. CONCLUSIONS: In summary, we have shown a direct activating activity of eosinophils, partially due to MBP, toward IgE-challenged and immunologically desensitized mast cells. This suggests that in vivo mast cells can be reactivated during a late-phase reaction to release histamine by a non-IgE-dependent mechanism.

Animals↗
PubMed1996

Blockade of multiple costimulatory receptors induces hyporesponsiveness: inhibition of CD2 plus CD28 pathways.

T-lymphocyte activation requires engagement of the T cell receptor with antigen-major histocompatibility complex, and simultaneous ligation of costimulatory pathways via the lymphocyte receptors CD2 and CD28/ CTLA4. Anti-CD2 monoclonal antibody (mAb) blocks the interaction of the antigen-presenting cell receptor CD48 with its ligand CD2, whereas CTLA4Ig binds with high affinity to the antigen-presenting cell ligands B7-1 and B7-2, blocking their interaction with CD28/CTLA4. We tested the immunosuppressive effects of simultaneously blocking both costimulatory pathways. Using donor C57BL/6J (H2b) hearts transplanted to CBA/J (H2k) recipients, anti-CD2 mAb plus CTLA4Ig administered at the time of transplantation prolonged cardiac allograft mean survival time to >120 days compared with untreated controls (12.2+/-0.5 days, P<0.01), anti-CD2 mAb alone (24.8+/-1.0 days, P<0.01), or CTLA4Ig alone (55.0+/-2.0 days, P<0.01). Retransplantation of these recipients with donor-specific and third-party grafts demonstrated that hyporesponsiveness and tolerance were achieved. In vitro stimulation of lymphocytes from tolerant recipients with donor-specific alloantigen resulted in normal cytotoxic T lymphocyte and mixed lymphocyte reaction responses, showing that clonal deletion or anergy did not occur, but that graft adaptation or suppression likely helped to maintain long-term graft survival. In vitro combinations of anti-CD2 mAb and CTLA4Ig suppressed the generation of allogeneic cytotoxic T lymphocytes (58%) and the mixed lymphocyte reaction (36%); CTLA4Ig was more effective in this regard and the two agents were not synergistic. Anti-CD2 mAb and CTLA4Ig suppressed mitogen-driven proliferation in differential fashions, suggesting that they affected independent signaling pathways. Anti-CD2 mAb and CTLA4Ig also inhibited interleukin (IL)-2, IL-4, and IL-2 receptor (CD25). These data indicate that anti-CD2 mAb plus CTLA4Ig induces hyporesponsiveness and tolerance. The mechanism is likely related to the initial disruption of independent pathways of T-lymphocyte activation leading to antigen-specific long-term graft survival.

Abatacept↗
PubMedDate not supplied

Research on a new type of antiinsulin antibody in a diabetic female patient: the cytotoxic antibody. antiinsulin cytotoxic antibody.

A study was carried out on a diabetic patient showing allergy to insulin, with urticaria and Quincke's edema, apparently owing to sensitization with IgE antibodies. By means of a hyposensitizing treatment her allergy improved due to the building up of IgG protecting antibodies, but at the same time she showed resistance to insulin, probably owing to IgG antibodies as well. This suggest that caution should be exerted before applying hyposensitization with insulin on diabetic patients allergic to the hormone. We were able to describe on the same patient a type II sensitization caused by a cytotoxic antibody against insulin. It was shown that this antibody agglutinates leukocytes which had been previously incubated with insulin and damage occurred when complement was present. Those effects could be especifically inhibited when the antigen (insulin) was added to the medium. The antibody belongs to the IgG group and it acts both in vivo and in vitro. In the case under study, the cytotoxic antibody disappeared as soon as treatment with insulin was discontinued for a year, and reappeared when renewed. It does not seem to occur very frequently, for it was not found in 20 consecutive diabetic patients under insulin treatment.

Aged↗
PubMedDate not supplied

Better documentation through standardized forms: what progress have we made since the 1800s?

It has been over a century since allergy skin testing and immunotherapy were first utilized. Both have withstood the test of time and numerous challenges such as cromolyn, antihistamines, and leukotriene modifiers that have threatened to make them obsolete, to continue to play a prominent role in the diagnosis and treatment of the allergic patient. Considerable advances in the understanding of immunotherapy mechanisms and effective allergen dosing as well as improved extract quality have been made in recent years. However, there appears to be a lag in the widespread implementation of these advances into clinical practice, where a broad wide range of practice patterns exists. The wide diversity of allergy practice patterns is likely because of the absence of a uniform curriculum in allergy and immunology training programs. Recently, practice parameters have been developed by the American Academy of Allergy, Asthma and Immunology' Immunotherapy Committee and the Joint Task Force on Practice Parameters, an organization that represents the American Academy of Allergy, Asthma, and Immunology and American College of Allergy, Asthma, and Immunology, aimed at promoting a consistent, objective scientific approach to allergy skin testing and immunotherapy. Standardized allergy skin test and immunotherapy forms were designed to incorporate these guidelines. The following article summarizes the recommendations of the practice parameters and reviews some of the clinical evidence that lends support to these guidelines, which are intended to enhance the safety and efficacy of allergy skin testing and immunotherapy.

Allergens↗