Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
-
Serum amyloid A (SAA), a precursor of reactive amyloid deposits, is a multigene product. SAA1, predominant both as an amyloid precursor and in plasma, consists of three allelic variants (SAA1.1, SAA1.3, and SAA1.5). Several investigations have shown that the SAA1.3 allele is associated with susceptibility to AA-amyloidosis in Japanese, and the SAA1.5 allele is related with higher serum concentrations of SAA. ⋯ The affinity (kd) of SAA1.1, SAA1.3, and SAA1.5 for HDL was 1.4 x 10(-5), 1.8 x 10(-5), and 3.7 x 10(-6), respectively. rSAA1.5 showed significantly (p < 0.05) stronger affinity than the other two. The fraction of lipid-free SAA in serum was significantly (p < 0.001) lower in the patients with larger numbers of the 1.5 allele at the SAA1 locus. These results suggest that the relatively high affinity of SAA1.5 may cause the high serum concentration and may be related to the low susceptibility to amyloidosis.
-
AL-Base, a curated database of human immunoglobulin (Ig) light chain (LC) sequences derived from patients with AL amyloidosis and controls, is described, along with a collection of analytical and graphic tools designed to facilitate their analysis. AL-Base is designed to compile and analyse amyloidogenic Ig LC sequences and to compare their predicted protein sequence and structure to non-amyloidogenic LC sequences. Currently, the database contains over 3000 de-identified LC nucleotide and amino acid sequences, of which 433 encode monoclonal proteins that were reported to form fibrillar deposits in AL patients. ⋯ Currently, tools are available to search for sequences by various criteria, to analyse the biochemical properties of the predicted amino acids at each position and to display the results in a graphical fashion. The likelihood that each sequence has evolved through somatic hypermutation can be predicted using an automated binomial or multinomial distribution model. AL-Base is available to the scientific community for research purposes.
-
A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of amyloidogenic immunoglobulin light chains.
-
Serum transthyretin (TTR) levels are reduced in familial amyloidotic polyneuropathy (FAP). A single study of patients with senile systemic amyloidosis (SSA) in Sweden found that those individuals also had a significantly lower mean serum TTR concentration than age- and gender-matched controls. To determine if the same phenomenon prevailed in an ethnically more heterogeneous population, we compared the serum TTR levels, as determined by ELISA, in 45 documented SSA patients with congestive heart failure, 20 AL patients with congestive heart failure and population controls. ⋯ We also compared TTR concentrations in 12 African-Americans carrying the TTR V122I allele with those in 826 African-Americans who were homozygous wild type at the TTR locus. The TTR V122I carriers had significantly lower serum TTR concentrations than appropriate controls even though the majority of such individuals had not reached the age of clinical or anatomic risk, i.e. over 60. Thus, as in carriers of other TTR mutations the serum TTR level is lower than normal, despite having a much later appearance of clinical disease.
-
Transthyretin (TTR) familial amyloid polyneuropathies (FAP) are autosomal dominant devastating afflictions. They were first described in Portugal, later in Japan and Sweden and are now recognized worldwide. The TTR Val30Met mutation is the most common, and depending on the geographic origin, a wide variation in age at onset of the disease is observed. ⋯ Differences between Piteå and Skellefteå regions were observed. Moreover, penetrance was significantly higher when the mutation was inherited from the mother than from the father. The low penetrance observed in TTR FAP kindreds and its variations is important information for the genetic counseling and treatment of Swedish FAP patients and their families.