title: Abatacept may be effective and safe in patients with amyloid A amyloidosis secondary to rheumatoid arthritis.
abstract: OBJECTIVE
  To examine the efficacy and safety of abatacept (ABT) in patients with amyloid A (AA) amyloidosis secondary to rheumatoid arthritis (RA), and to speculate about the immunologic association of ABT with AA amyloid deposit regression.
  
  
  METHODS
  We administered ABT to 70- and 65-year-old Japanese women with RA and AA amyloidosis. We quantified serum cytokine concentrations and analysed regulatory T lymphocytes (Treg cells) via flow cytometry. We also studied AA amyloid deposits via histopathology and immunohistochemistry.
  
  
  RESULTS
  ABT improved rheumatoid inflammation and AA amyloidosis, one case showing clinical remission and the other demonstrating incomplete recovery of nephrosis but stable kidney function. Serum levels of interleukin-6 and tumour necrosis factor α decreased to baseline in the first 6 months of treatment, but serum interleukin-2 concentrations did not change. CD4+CD25++FoxP3+ Treg cells gated on T lymphocytes and CD4+ T lymphocytes decreased to baseline in the first 3 treatment months. One case showed complete regression of AA amyloid fibrils in serial upper gastrointestinal biopsies, but the other case still had AA amyloid deposits despite ABT-induced normalised rheumatoid inflammation, with polymorphonuclear leukocytes and macrophages infiltrating tissues containing AA amyloid.
  
  
  CONCLUSIONS
  ABT demonstrated efficacy and safety in AA amyloidosis secondary to RA and affected Treg cells and inflammatory cytokines. Because the gradual decrease in Treg cells population coincided with AA amyloid deposit regression during ABT therapy, AA amyloid fibril turnover in these patients may involve an immunologic mechanism. Phagocytes seemed to have an important role in AA amyloid fibril regression, which suggests an immunologic interaction.
authors: Clinical Rheumatology, Kumamoto Shinto General Hospital, Kumamoto, Japan. nakamura@k-shinto.or.jp.
authors: Tadashi
authors: T
authors: Nakamura
authors: Yoshitaka
authors: Y
authors: Kumon
authors: Shinya
authors: S
authors: Hirata
authors: Hirokazu
authors: H
authors: Takaoka
mesh_terms: D000069594:Abatacept; D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D018796:Immunoconjugates; D000685:Serum Amyloid A Protein; D000069594:Abatacept