Amyloidosis and Auto-Inflammatory Syndromes

Abstract

Amyloidosis remains currently a severe potential complication of many chronic inflammatory disorders. It is not exactly know why some patients develop a progressive amyloidosis, whereas others do not although latent deposits may be present. A permanent acute phase response, ideally evaluated with serial measurement of serum protein SAA, the precursor of the AA protein deposited in tissues, seems to be a prerequisite to the development of inflammatory (AA) amyloidosis. Genetic factors have however been recently emphasized. Among persistent or emerging causes of AA amyloidosis, hereditary periodic fever syndromes also known as auto-inflammatory syndromes are a group of diseases characterised by intermittent bouts of clinical inflammation with focal organ involvement mainly: abdomen, musculoskeletal system and skin. The most frequent is familial Mediterranean fever which affects patients of Mediterranean descent all over the world. Three other types have been recently clinically as well as genetically characterised. A thorough diagnosis is warranted, as clinical and therapeutic management is specific for each of these diseases.

Clinical and histological characteristics of renal AA amyloidosis: a retrospective study of 68 cases with a special interest to amyloid-associated inflammatory response

“…Amyloid A protein fragments have thus different sizes and specific biochemical properties, especially variations of their isoelectric focusing point, leading to a different tissue distribution. Moreover, the risk to develop amyloidosis is different according to the SAA1 genotype, 1 of the 2 genes encoding for the acute phase serum amyloid A proteins (ie, SAA1 and SAA2) [17,18]. The biochemical properties of AA proteins would explain both their amyloidogenicity and their different organ distribution leading to different clinical manifestations and renal outcome.…”

Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis

“…A paradigm shift in RA therapies within the window of therapeutic opportunity would bring about clinical remission of AA amyloidosis [57]. Convalescence will result in abolishing the accompanying acute-phase response and thereby preventing the development of AA amyloidosis [58]. In light of the importance of the SAA1.3 allele in patients with AA amyloidosis secondary to RA [37], it is emphasized that RA patients carrying the SAA1.3 allele should be followed up carefully.…”

Causal or Causal Relationship Between Oral Diseases and Systemic Amyloidosis – From Inflammation to Amyloidosis – A Trouble Connection

“…Hereditary systemic amyloidoses are a group of autosomal dominant disorders caused by mutations in the genes of several plasma proteins. In this section, we focus on the more common of these conditions, which are systemic AA amyloidosis, oral focal infections especially chronic periodontitis, and familial amyloidosis especially autoinflammatory diseases (Glenner, 1980;Kisilevski, 1992;Grateau et al, 2005). Systemic AA amyloidosis, representing approximately 45 percent of generalized amyloidoses are inflammatory arthritis (Rheumatoid arthritis), chronic infections (Bronchiectasis, tuberculosis, chronic cutaneous infections, osteomyelitis), Immunodeficiency status, other conditions predisposing to chronic infections (Injected drug abuse, epidermolysis bullosa, paraplegia), Hereditary periodic fevers (Familial Mediterranean fever, Hyperimmunglobulin D syndrome, TNF receptor-associated periodic syndrome), Inflammatory bowel disease (Crohn's disease, ulcerative colitis), Neoplasia, Systemic vasculitis (Behçet's disease, systemic lupus erythematosis), others (Sarcoidosis).…”