scholarly journals Humoral Immune Responses of Type 1 Diabetes Patients to Mycobacterium avium subsp. paratuberculosis Lend Support to the Infectious Trigger Hypothesis

2007 ◽  
Vol 15 (2) ◽  
pp. 320-326 ◽  
Author(s):  
Leonardo A. Sechi ◽  
Valentina Rosu ◽  
Adolfo Pacifico ◽  
Giovanni Fadda ◽  
Niyaz Ahmed ◽  
...  

ABSTRACT Mycobacterium avium subsp. paratuberculosis is a zoonotic pathogen whose association with Crohn's disease in humans is under scrutiny. The objective of this work was to investigate its association with other chronic diseases such as type 1 diabetes mellitus (T1DM), where the involvement of a persistent pathogen such as M. avium subsp. paratuberculosis could be the trigger. For this purpose, 59 diabetic patients and 59 healthy controls were investigated for the presence of antibodies against two recombinant proteins of M. avium subsp. paratuberculosis and the whole-cell lysate. Extremely significant humoral immune responses to recombinant heparin binding hemagglutinin and glycosyl transferase proteins and the whole-cell lysates of M. avium subsp. paratuberculosis bacilli were observed in T1DM patients and compared to those of healthy controls. Finding evidence of M. avium subsp. paratuberculosis involvement in T1DM is perhaps a novel finding that might serve as a foundation stone in establishing an infectious etiology for T1DM.

Diabetes Care ◽  
2013 ◽  
Vol 36 (11) ◽  
pp. 3418-3424 ◽  
Author(s):  
S. Axelsson ◽  
M. Cheramy ◽  
L. Akerman ◽  
M. Pihl ◽  
J. Ludvigsson ◽  
...  

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 729
Author(s):  
Leah E. Cole ◽  
Jinrong Zhang ◽  
Kristl M. Pacheco ◽  
Philippe Lhéritier ◽  
Natalie G. Anosova ◽  
...  

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting.


2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.


2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.


2003 ◽  
Vol 19 (4) ◽  
pp. 293-305 ◽  
Author(s):  
Thippawan Chuenchitra ◽  
Chantapong Wasi ◽  
Suda Louisirirojchanakul ◽  
Sorachai Nitayaphan ◽  
Ruengpung Sutthent ◽  
...  

2004 ◽  
Vol 78 (13) ◽  
pp. 7061-7068 ◽  
Author(s):  
Wendy Fitzgerald ◽  
Andrew W. Sylwester ◽  
Jean-Charles Grivel ◽  
Jeffrey D. Lifson ◽  
Leonid B. Margolis

ABSTRACT Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4+ T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4+ T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4+ T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.


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