Shoulder‐Pad Sign of Amyloidosis: Structure of an Ig Kappa III Protein

Abstract

While amyloid infiltration of articular structures is rare, the`shoulder-pad' sign resulting from periarticular soft tissue amyloid deposition is essentially pathognomonic for immunogloblin (Ig) (AL) amyloidosis. We report the characterization of an amyloid protein (GRA) which produced articular amyloid deposits and the shoulder-pad sign. Amyloid fibrils were isolated from soft tissue shoulder mass of a patient with systemic AL amyloidosis. The fibrils were solubilized in guanidine HCl and proteins separated by Sepharose chromatography. Amino acid sequence of fractionated protein was determined after tryptic digestion. Sequence analysis of the major amyloid protein yielded a kappa III Ig light chain structure. The entire variable region (V L ) plus the constant region (C L ) to residue 207 was identified; but lesser amounts of C L than V L were present. A number of amino acid residues previously not observed in kappa III V L proteins, plus a two amino acid insert (95A, 95B), were identified. Kappa III V L amyloid proteins are rare and may show an increased predilection for soft tissue deposition. While several unique amino acid residues that were identified in protein GRA may contribute to soft tissue amyloid deposition, no definite pattern is obvious from comparison with other reported kappa III amyloid proteins.

Soft tissue, joint, and bone manifestations of AL amyloidosis: Clinical presentation, molecular features, and survival

“…A trend toward an association of V L κI gene usage and primary soft tissue disease has previously been reported (37). In another study, V L κIII protein was isolated from the shoulder tissue of a patient with dominant soft tissue and bone involvement (14). None of the V L sequences in our group of patients with dominant soft tissue and bone involvement and articular involvement were of the V L κIII type (Table 3), and the predicted protein sequences did not encode the amino acids at positions 32, 34, 59, and 95 that were present in the V L κIII protein.…”

“…Dominant soft tissue and bone involvement has been thought to be a relatively indolent presentation of AL amyloidosis (14). Our survival data did demonstrate an improved median survival time and higher rate of early survival among patients with dominant soft tissue and bone involvement compared with those with other dominant organ involvement.…”

“…CTS was defined by the examining neurologist on the basis of history, presence of Tinel's sign or Phalen's sign, electrophysiologic changes, or based upon pathologic finding of Congo red–positive material in tissue obtained during surgical release. Of note, macroglossia and the “shoulder pad” sign caused by periarticular soft tissue deposition of amyloid fibrils were pathognomonic for AL amyloidosis (14); the other manifestations were less specific.…”

“Eyeing” the Cause of Heart Failure: Visible Telltale Clues

“…Such a "shoulder-pad" sign results from periarticular deposition of amyloid and is essentially pathognomonic of the disease. 18 The shoulders and surrounding structures, including the muscles, become markedly swollen and rubbery hard but not tender. This patient also had a distinctly enlarged tongue 18 and rapidly progressive heart failure, 19 both of which left no doubt about the diagnosis.…”

“…18 The shoulders and surrounding structures, including the muscles, become markedly swollen and rubbery hard but not tender. This patient also had a distinctly enlarged tongue 18 and rapidly progressive heart failure, 19 both of which left no doubt about the diagnosis. Proof came at autopsy, which showed dense deposits of amyloid throughout her body, especially in her heart, kidneys, muscles, periarticular tissue, and vasculature.…”