Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An association between humoral immune deficiency and childhood autoimmune disease has been previously established. We describe a 7-year-old male with severe autoimmune disease, recurrent infections, a marked deficiency of IgG2 and IgG4, and an inability to respond to polysaccharide antigens. This child was also found to have isolated growth hormone (GH) deficiency. Laboratory results included a positive anti-smooth muscle antibody, a positive Raji-cell assay for immune complexes, and normal levels of IgG, IgM, and IgA. IgG subclasses revealed an IgG1 of 1225 (normal for age, 280-1120 mg/dl), IgG2 of less than 10 (30-630 mg/dl), IgG3 of 36 (40-250 mg/dl), and IgG4 of less than 4 (11-620 mg/dl). No increase in antibody titer was noted to either Pneumovax or unconjugated Haemophilus influenzae vaccine. Numbers of circulating B cells (CD19) were markedly diminished (less than 0.5%). Liver biopsies have shown chronic active hepatitis. Somatomedin C was 0.28 U/ml (normal for age, 0.5-2.06 U/ml). Challenge with either L-dopa or clonidine produced a peak GH response of 2.3 ng/ml (normals = greater than 7 ng/ml). Children with autoimmune disorders should be evaluated for IgG subclass deficiencies and ability to make antibody in response to antigen challenge regardless of the serum immunoglobulin levels. Growth failure in immune-deficient children should not be assumed to be due to chronic illness or recurrent infections. Other etiologies for growth failure should be sought.
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PMID:Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child. 208 46

Twelve patients with skin vasculitis complicating cystic fibrosis are described. Seven of these were proven histologically and of these two had systemic vascultitis. Staining of vasculitic tissue by the avidin-biotin immunoperoxidase technique using both monoclonal and polyclonal antisera directed against Haemophilus influenzae, staphylococcus aureus and Pseudomonas aeruginosa did not consistently reveal any bacterial antigens in these tissues. In one patient the vasculitis appeared secondary to ranitidine. There was no evidence of autoimmune disease in any of the patients. Antineutrophil cytoplasmic antibodies were detected in the serum of 40 per cent of the patients with vasculitis complicating cystic fibrosis but in none of 61 controls with cystic fibrosis (but without vasculitis) matched for age and sex and with similar bacteriological flora of sputum.
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PMID:Vasculitis complicating cystic fibrosis. 260 80

The tyrosine phosphatase IA-2 is a molecular target of pancreatic islet autoimmunity in type 1 diabetes. T-cell epitope peptides in autoantigens have potential diagnostic and therapeutic applications, and they may hold clues to environmental agents with similar sequences that could trigger or exacerbate autoimmune disease. We identified 13 epitope peptides in IA-2 by measuring peripheral blood T-cell proliferation to 68 overlapping, synthetic peptides encompassing the intracytoplasmic domain of IA-2 in six at-risk type 1 diabetes relatives selected for HLA susceptibility haplotypes. The dominant epitope, VIVMLTPLVEDGVKQC (aa 805-820), which elicited the highest T-cell responses in all at-risk relatives, has 56% identity and 100% similarity over 9 amino acids (aa) with a sequence in VP7, a major immunogenic protein of human rotavirus. Both peptides bind to HLA-DR4(*0401) and are deduced to present identical aa to the T-cell receptor. The contiguous sequence of VP7 has 75% identity and 92% similarity over 12 aa with a known T-cell epitope in glutamic acid decarboxylase (GAD), another autoantigen in type 1 diabetes. This dominant IA-2 epitope peptide also has 75-45% identity and 88-64% similarity over 8-14 aa to sequences in Dengue, cytomegalovirus, measles, hepatitis C, and canine distemper viruses, and the bacterium Haemophilus influenzae. Three other IA-2 epitope peptides are 71-100% similar over 7-12 aa to herpes, rhino-, hanta- and flaviviruses. Two others are 80-82% similar over 10-11 aa to sequences in milk, wheat, and bean proteins. Further studies should now be carried out to directly test the hypothesis that T-cell activation by rotavirus and possibly other viruses, and dietary proteins, could trigger or exacerbate beta-cell autoimmunity through molecular mimicry with IA-2 and (for rotavirus) GAD.
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PMID:T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. 960 76

Homozygous deficiency of the second component of complement (C2) is the most common inherited deficiency of complement. Although C2 deficiency has been detected in asymptomatic individuals, patients usually present with either autoimmune disease or recurrent pyogenic infection, particularly due to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis. Interestingly, infection is the most common mode of presentation of C2 deficiency in young children (1). An association between C2 deficiency and IgG subclass deficiency has also been previously described. We now report a female child with C2 deficiency that presented at the age of 3 mo with recurrent pneumococcal septicaemia. Although IgG subclass levels were normal, specific IgG responses to vaccination against S. pneumoniae and H. influenzae were significantly impaired.
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PMID:Impaired IgG responses in a child with homozygous C2 deficiency and recurrent pneumococcal septicaemia. 1122 45

It has been known for many years that bacteria can induce autoimmune responses in humans resulting in serious disease. Recent work has shown that a number of bacteria that colonize human mucosal surfaces exclusively express antigens on their surfaces which are molecular mimics of glycosphingolipids found on human cells. These structures are important in the pathogenesis of Neisseria and Haemophilus species for both immune evasion and in the adherence and invasion of human cells. There is no evidence that colonization or infections by these bacterial species is associated with autoimmune disease.
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PMID:The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus. 1133 90

Molecular mimicry is the main postulated mechanism by which infectious agents induce autoimmune disease. A number of animal models have been utilized to establish a link between molecular mimicry and autoimmunity. However, a model of infectious disease whereby a natural pathogen expressing a known mimic epitope can induce autoimmunity to a known self-antigen leading to clinical autoimmune disease is still lacking. We have engineered a recombinant Theiler's murine encephalomyelitis virus (TMEV) to express an encephalitogenic myelin proteolipid protein PLP139-151 epitope (PLP-TMEV) and a PLP139-151 mimic peptide naturally expressed by Haemophilus influenzae (HI-TMEV). Infection of mice with either PLP-TMEV or HI-TMEV induces early-onset disease that is associated with the activation of cross-reactive PLP139-151-specific immunopathologic CD4+ Th1 cells. Based on results from this model, we hypothesize, due to the considerable degeneracy in the T cell repertoire, that induction of full-blown autoimmune disease via molecular mimicry is a tightly regulated process requiring multiple factors related to the pathogen expressing the potential mimic epitope. In this review, we will discuss how various factors related to the infectious environment control whether or not autoimmune disease is initiated. Contributing factors include the nature of the innate immune response to the pathogen which determines the immunopathologic potential of the induced cross-reactive T cells, the capacity of the mimic epitope to be processed and presented from its natural flanking sequences in the pathogen-encoded protein, the site(s) of the primary infection in the host and the ability of the pathogen to persist, and the potential requirement for multiple infections with the same or different pathogens.
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PMID:Innate and adaptive immune requirements for induction of autoimmune demyelinating disease by molecular mimicry. 1503 15

Epidemiological studies indicate that infectious agents are important in the pathogenesis of multiple sclerosis (MS). Our previous reports showed that the infection of SJL mice with a nonpathogenic variant of Theiler's murine encephalomyelitis virus (TMEV) engineered to express a naturally occurring Haemophilus influenzae-encoded molecular mimic (HI574-586) of an immunodominant self-myelin proteolipid protein epitope (PLP139-151) induced a rapid-onset demyelinating disease associated with the activation of PLP139-151-specific Th1 responses. The current results extend our previous findings in four critical respects. We show that disease initiation by the H. influenzae mimic is prevented by tolerance to the self PLP139-151 epitope, definitively proving the occurrence of infection-induced molecular mimicry. We demonstrate that the H. influenzae mimic epitope can be processed from the flanking sequences within the native mimic protein. We show that the H. influenzae mimic epitope only induces an immunopathologic self-reactive Th1 response and subsequent clinical disease in the context of the TMEV infection and not when administered in complete Freund's adjuvant, indicating that molecular mimicry-induced disease initiation requires virus-activated innate immune signals. Lastly, we show that the infection of SJL mice with TMEV expressing the H. influenzae mimic can exacerbate a previously established nonprogressive autoimmune disease of the central nervous system. Collectively, these findings illustrate the evolving mechanisms by which virus infections may contribute to both the initiation and exacerbation of autoimmune diseases, and they have important implications for MS pathogenesis.
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PMID:Initiation and exacerbation of autoimmune demyelination of the central nervous system via virus-induced molecular mimicry: implications for the pathogenesis of multiple sclerosis. 1595 99

Multiple sclerosis1 (MS) is an immune-mediated autoimmune demyelinating disease in humans. The initiating event in MS is unknown, but epidemiological evidence suggests that virus infections may be important and one possible mechanism for induction of infection-induced autoimmune disease is molecular mimicry. To test the ability of a virus encoding a self myelin mimic epitope to induce an autoimmune response, we have developed a mouse model wherein the immunodominant myelin epitope PLP139-151, or mimics of this epitope, were inserted into a nonpathogenic variant of Theiler's murine encephalomyelitis virus (TMEV). SJL mice infected with TMEV containing PLP139-151 or a mimic of PLP139-151 expressed by the protease IV protein of Haemophilus influenzae, sharing only 6/13 amino acids with the native epitope, developed an early-onset demyelinating disease associated with activation of CD4+ T cells reactive with PLP139-151. We have used this molecular mimicry model to further address the requirements for mimic epitope processing and presentation during infection and the requirements for TCR recognition and MHC binding of mimic epitopes. We have also investigated whether molecular mimicry may require multiple infections, with either the mimic-encoding virus or an unrelated virus, to initiate autoimmune disease. Finally, we have asked whether a virus encoding a molecular mimic has to directly infect the target organ to induce autoimmune disease. Overall, this virus-induced molecular mimicry model has provided critical information regarding the mechanisms by which infection-induced molecular mimicry can induce autoimmune diseases.
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PMID:A virus-induced molecular mimicry model of multiple sclerosis. 1632 19

MS is an autoimmune CNS demyelinating disease in which infection appears to be an important pathogenic factor. Molecular mimicry, the cross-activation of autoreactive T cells by mimic peptides from infectious agents, is a possible explanation for infection-induced autoimmunity. Infection of mice with a non-pathogenic strain of Theiler's murine encephalomyelitis virus (TMEV) engineered to express an epitope from Haemophilus influenzae (HI) sharing 6/13 amino acids with the dominant proteolipid protein (PLP) epitope, PLP139-151, can induce CNS autoimmune disease. Here we demonstrate that another PLP139-151 mimic sequence derived from murine hepatitis virus (MHV) which shares only 3/13 amino acids with PLP139-151 can also induce CNS autoimmune disease, but only when delivered by genetically engineered TMEV, not by immunization with the MHV peptide. Further, we demonstrate the importance of proline at the secondary MHC class II contact residue for effective cross-reactivity, as addition of this amino acid to the native MHV sequence increases its ability to cross-activate PLP139-151-specific autoreactive T cells, while substitution of proline in the HI mimic peptide has the opposite effect. This study describes a structural requirement for potential PLP139-151 mimic peptides, and provides further evidence for infection-induced molecular mimicry in the pathogenesis of autoimmune disease.
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PMID:Structural requirements for initiation of cross-reactivity and CNS autoimmunity with a PLP139-151 mimic peptide derived from murine hepatitis virus. 1698 Nov 79

It has been postulated that infectious agents may precipitate autoimmune disease when T cell responses raised against the pathogen cross-react with self-peptides, a phenomenon known as molecular mimicry. However, there are very little data available characterizing the similarity between the repertoire of the cross-reactive self-specific T cell population compared with the pathogen-specific T cell repertoire. In this study, we use immunoscope analysis to identify the T cell populations induced upon priming SJL/J mice with a pathogen-derived mimic of the immunodominant encephalitogenic myelin peptide PLP(139-151), which is contained within the protease IV protein of Haemophilus influenzae (HAE(574-586)). We describe an IFN-gamma-producing Vbeta19(+) T cell population in HAE(574-586)-primed mice that appears to be the "public clonotype" as it expanded in response to peptide in all mice tested. Critically this Vbeta19(+) T cell population is not expanded in mice primed with the self-peptide PLP(139-151), indicating that mimics can induce the expansion of new self-reactive populations not initially present in the periphery of a host. This is the first description of the use of immunoscope analysis to characterize the cross-reactive anti-self T cell response induced by a molecular mimic.
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PMID:Molecular mimics can induce novel self peptide-reactive CD4+ T cell clonotypes in autoimmune disease. 1798 50


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