ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger

Abstract

Introduction

Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.

Methods

205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.

Results

Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.

Conclusion

Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.

Keywords:

• Annular ligament
• ATTR amyloid
• fibrinogen
• LC-MS/MS
• trigger finger

Author contributions

E.G. conducted tissue sample preparation, C.T. performed proteomics sample preparation and LC-MS experiments, C.T. and A.T. performed LC-MS data interpretation. C.T. provided Figures 3–5 and Supplementary Figures 2–4, and Supplementary Tables 1; N.M.M. and C.R. performed histological and immunohistochemical studies of the study cohort; N.M.M., and C.R. provided Figures 1, 2. R.R.M., P.U., H.D.A., F.S., K.B., and K.M. provided tissue samples and clinical patient data. C.R., P.U. and R.R.M. carried out primary histological studies. All authors conceptualised and wrote the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Anonymized data are available on request from the senior author.

Data deposition

LC-MS data were deposited to the ProteomeXchange Consortium via the PRIDE partner repository [13] with the dataset identifier PXD039511.

Additional information

Funding

(A.T.): Deutsche Forschungsgemeinschaft (DFG) - Cluster of Excellence ‘Precision Medicine in Inflammation’, RTF-V. (C.R.): Deutsche Forschungsgemeinschaft (DFG; Grant No. Ro 1173/14; FOR 2969/0).