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Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
Pathogenetic issues of IgG4 related diseases
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Pathogenetic issues of IgG4 related diseases

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presented in kolkata on 24th december 2013

presented in kolkata on 24th december 2013

Published in: Health & Medicine, Technology
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  • 1. Speaker Dr. Dibbendhu Khanra Chairperson Dr. Debasish Basu
  • 2. 44 M: Thailand Asthmatic 54 M: Indian Atopic dermatitis 64 M: Japanese Ascites/ Pedal edema Sjogren’s syndrome Lymphoma SSA/B, Bx –ve, CA pancreus CA 19-9 –ve Bx- nonmalignant B/L Hydronephrosis IVC obstruction Retroperitoneal fibrosis What is common?
  • 3. What is common? Clinically Serologically Pathologically  Male  Asian  Age _ 50  Tumor  Allergy  Serum globin more  Serum IgE more  Serum IgG more  Fibrosis  Lymphoplasmcytosis  No granuloma Outcome Good Response To Steroids Are we chasing a chameleon?
  • 4. History and evolution N Engl J Med 2012;366:539-51
  • 5. IgG4 related diseases Atac et al. The rheumatologists 2013
  • 6. Pathogenetic issues of IgG4 related diseases  what’s wrong with IgG4?  why common in Asians?  autoimmune/ allergic/ infective disease?  constitutional symptoms?  why multifocal fibro-inflammation?
  • 7. IgG4 Fc-Fc interaction with other IgG4 antibodies Inter-heavy chain disulfide bond formation Half antibody/ (Fab)–arm exchange Asymmetric bi-specific antibody formation  Negligible binding to C1q & Fcγ receptors. Does not activate complement pathway.  Unable to crosslink antigens, thereby losing the ability to form immune complexes  IgG4 is an anti-inflammatory antibody N Engl J Med 2012;366:539-51
  • 8.  Male (60-80%)  Asian  >50 years IgG4 related diseases: Potential Triggers  HLA DRB1*0405 (Japanese)  HLA DQβ1-57 (Korean) Auto-antibodies directed against antigens expressed in various exocrine organs H. Pylori has been linked to AIP (molecular mimicry) N Engl J Med 2012;366:539-51
  • 9. IgG4 related diseases: IgG4 class switch V/S allergic diseases Allergic association (40%) IgG4 deposits are not pathogenic V/S autoimmune diseases Fibroinflammation N Engl J Med 2012;366:539-51 Lack of constitutional symptoms
  • 10. IgG4 related diseases: Cellular response Plasma cells (IgG4 +ve) T cells more V/S Malignancy: B cell Lymphoma Tumefactive enlargement of organs or sites It is unclear whether these organ dysfucntion are due to immune complex–mediated tissue damage or are a bystander phenomenon So, not all IgG4 looses bispecificity
  • 11. IgG4 related diseases A new entity New understanding of an existing disease Multiple diseases under the umbrella of same pathogenesis/ pathology
  • 12. IgG4 related diseases       Asian, male, >50 years multi-organ involvement subacute mass-like with compression lymphadenopathy lack of constitutional symptoms    Polyclonal hyper-gammaglobulin  serum IgG4 high (70%)  tissue IgG4/ serum IgG4>50%  Serum IgE may be high (40%)  allergic assocaitions (40%)  ANA positive (30%) Lymphoplasmacytic infiltaration. IgG4 positive. Neutrophils rare. Patterned Fibrosis: “storiform”, “cartwheel” No necrosis, No granuloma  often self-limiting; watchful waiting is prudent  good response with steroids  increased risk of lymphoma and other malignancy
  • 13. IgG4 related diseases – chasing a chameleon Mickulitz syndrome AIP Ormond’s disease Retroperitoneal fibrosis Divided by presentation; united by histology
  • 14. Pathogenetic issues: Demystified  what’s wrong with IgG4?  sine-qua-non but not pathological  why common in Asians?  HLA associations  autoimmune/ allergic/ infective disease?  None; fibro inflammatory  why no constitutional symptoms?  Localized depositions  why multifocal fibro-inflammation?  most important cell – T reg cells  most important molecule – TGFb  most important by-product – IgG4
  • 15. When, in the wrong place, there is something, that’s disorder. When, in the right place, there is nothing, that’s order - Brecht Thank you

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