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Salvatore Benvenga - One of the best experts on this subject based on the ideXlab platform.
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Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons. 2010 Springer Science+Business Media, LLC
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Reply: Does clostridium botulinum neurotoxin a exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.
Eduardo J. Yunis - One of the best experts on this subject based on the ideXlab platform.
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HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy.
Journal of Immunology, 1992Co-Authors: Malcolm N. Blumenthal, Zuheir L. Awdeh, Eduardo J. Yunis, Deborah Marcus-bagley, Beatrice Johnson, Chester A AlperAbstract:MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only.
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Association of polymorphisms in the HLA-B region with extended haplotypes
Immunogenetics, 1991Co-Authors: Gloria E. Egea, Zuheir L. Awdeh, Chester A Alper, Ivan Yunis, Thomas Spies, Jack Strominger, Eduardo J. YunisAbstract:Genomic probes from the HLA-B region of the major histocompatibility complex (MHC) were used to study the association of restriction fragment length polymorphisms (RFLPs) with various MHC alleles, complotypes, and extended haplotypes. The two DNA probes, M20A and R5A, were derived from previously cloned cosmids and are located 38 and 110 kilobases (kb) centromeric to HLa-B , respectively. Five different RFLP variants occuring in five different haplotypic combinations were detected within a panel of 40 homozygous-typing cells and cells from 21 families using Bst EII. In two informative families with HLA-B/DR recombinations the inheritance of the RFLP variants was consistent with their mapping between HLA-B and complotypes. The R5A/M20A haplotypic pattern 6.5 kb/3.0 kb (A) had a normal Caucasian frequency of approximately 0.43 and was found in all independent examples of the extended haplotypes [ HLA-B8,SC01,DR3 ], [ HLA-B18,F1C30, DR3 ], [ HLa-Bw62,SC33,Dr4 ], [ HLa-B44,SC30,Dr4 ], and [ HLA-Bw47,FC91,0DR7 ]. The patterns of 6.9 kb/ 3.0 kb (B), 6.5 kb/4.7 kb (C), 1.45 kb/3.0 kb (D), and 6.9 kb/4.7 kb (E) had normal Caucasian frequencies of approximately 0.23, 0.15, 0.15, and 0.04 and were found on all independent examples of [ HLA-B38,SC21, DR4 ], [ HLA-Bw57,SC61,DR7 ], [ HLA-B7,SC31,DR2 ], and [ HLA-B44,FC31,DR7 ], respectively. Individual complotypes or HLA-B alleles which were markers of extended haplotypes showed variable associations. For example, HLA-B7 and the complotype SC31 were associated with all R5A/M20A RFLP haplotypes except haplotype E, although [ HLA-B7,SC31,DR7 ] was associated exclusively with haplotype D. HLA-B27 , not known to be part of an extended haplotype, was suprisingly exclusively associated with the 6.5 kb/4.7 kb or C haplotypic pattern in all five instances tested. These findings support the concept of regional conservation of DNA on independent examples of extended haplotypes. The results also further characterize these haplotypes.
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HLA-DQ RFLP variants of five HLA-DQw2-bearing major histocompatability complex extended haplotypes
Immunogenetics, 1990Co-Authors: Juan J. Yunis, Zuheir L. Awdeh, Chester A Alper, Mark Wescott, Scarlet J. Lechin, Sharon M. Alosco, Eduardo J. YunisAbstract:We have analyzed genomic DNA in a large number of independent examples of five HLA-DQw2 -bearing extended haplotypes for their associated subtypes by restriction fragment length polymorphism (RFLP) using DRB, DQA , and DQB probes after Taq I and Pst I digestion and Southern blotting. In addition to three previously described HLA-DQw2 subtypes, DQw2a , DQw2b , and DQw2c , we observed a fourth subtype, HLA-DQw2d , characterized by 5.8 kilobase (kb) DRB/Taq I, 2.4, 2.3, and 1.8 kb DQB/Taq I, and 8.0 and 2.3 kb DQA/Pst I fragments. All 22 independent examples of the extended haplotype [ HLA-B8,SCO1,DR3 ] carried DQw2a and all 11 independent examples of [ HLA-B18,F1C30,DR3 ] carried DQw2b . In addition, all independent examples (21 and 4, respectively) of two DR7 -carrying extended haplotypes, [ HLA-B44,FC31,DR7 ] and [ HLA-Bw47,FC91,0,DR7 ], carried DQw2c and all independent examples of [ HLA-Bw57,SC61,DR7 ] carried DQw2d . Our results show that the DNA in the DR/DQ region of extended haplotypes is relatively fixed and that different DQw2 subtypes characterize different DQw2 -bearing extended haplotypes.
Edvina Gregoric - One of the best experts on this subject based on the ideXlab platform.
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Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons. 2010 Springer Science+Business Media, LLC
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Reply: Does clostridium botulinum neurotoxin a exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.
Jurji Avramovic Gregoric - One of the best experts on this subject based on the ideXlab platform.
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Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons. 2010 Springer Science+Business Media, LLC
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Reply: Does clostridium botulinum neurotoxin a exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.
Fabrizio Guarneri - One of the best experts on this subject based on the ideXlab platform.
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Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons. 2010 Springer Science+Business Media, LLC
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Reply: Does clostridium botulinum neurotoxin a exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?
Endocrine, 2011Co-Authors: Edvina Gregoric, Jurji Avramovic Gregoric, Fabrizio Guarneri, Salvatore BenvengaAbstract:A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.