Clinical value of immunohistochemistry with AF-antibody in the diagnosis of familial amyloid neuropathy

Abstract

Peripheral polyneuropathy associated with recurrent diarrhoea and orthostatic hypotension was observed in two unrelated German kinships and two sporadic cases. Congo red staining and polarization microscopy of biopsy specimens revealed amyloid deposits. Immunohistochemical investigation using the indirect immunoperoxidase staining with antisera to several purified amyloid fibril proteins showed a positive reaction with an antiserum to the prealbumin-related AF-amyloid in the families and one of the sporadic cases and with an antiserum to the immunoglobulin light chain amyloid (A lambda) in the other sporadic case. Therefore, the amyloid of the families and one of the sporadic cases was identified as the prealbumin-related AF amyloid, while the amyloid of the other sporadic case was of immunoglobulin origin. It is concluded that immunohistochemistry with antisera to the different amyloid proteins is useful in the differential diagnosis of amyloid neuropathy.

Congo Red Staining of Amyloid: Improvements and Practical Guide for a More Precise Diagnosis of Amyloid and the Different Amyloidoses

“…Using antibodies against isolated and well-characterized prototype amyloid proteins, satisfactory results on formalin-fi xed paraffi n sections were achieved by three different groups using either an anti-AA antiserum and a not further specifi ed "anti-AL" antiserum (Levo et al, 1980) or anti-AA, anti-ALλ and anti-ALκ-antibodies (Fujihara et al, 1980;Linke and Nathrath, 1980;Fujihara and Glenner, 1981;Fujihara, 1982), or adding to this panel of three antibodies a fourth antibody, antiamyloid of transthyretin origin (ATTR), after Costa et al (1978) reported TTR as a new amyloid protein (Linke, 1982;Van de Kaa et al, 1986;Feurle et al, 1984;Dalakas et al, 1984). Applying this antibody panel to tissue sections of 122 unselected patients with systemic amylodoses, 120 (98%) could be identifi ed and classifi ed, demonstrating the feasibility of this approach for routine clinical amyloid typing of various amyloids .…”

“…With the discovery of more amyloid proteins this immunohistochemical option of a relatively easy and direct way of typing amyloid was extended, resulting in a panel of antibodies that could be applied to solve various questions concerning the classifi cation of amyloidoses in patients and in retrospective lists of various tissues using several immunohistochemical variants Casanova et al, 1992;Röcken et al, 1996aRöcken et al, , 1996bArbustini et al, 1997;Strege et al, 1998;DeCarvalho et al, 2004). In particular, amyloids in biopsies of neural tissue (Feurle et al, 1984;Staunton et al, 1987;Li et al, 1992;Jenne et al, 1996), cerebral tissue (Allsop et al, 1988;Kitamoto et al, 1987;Baron et al, 1988;Schröder et al, 1995;Schröder and Linke, 1999), carpal tunnel tissue (Stein et al, 1987;Kyle et al, 1992), endomyocardial bioptic tissue (Frenzel et al, 1986), lymph node tissue (Newland et al, 1986), laryngeal tissue (Godbersen et al, 1992), skin tissue (Bieber et al, 1988;Dithmar et al, 2004), and subcutaneous tissue (Orfi la et al, 1986) have been classifi ed on formalin-fi xed paraffi n sections. The identifi cation of amyloids can also be performed using peptide antibodies (Westermark et al, 1987(Westermark et al, , 1999Solomon et al, 2003a).…”

Pathophysiology of Diarrhea in Patients with Familial Amyloid Neuropathy

“…Five of these patients have been re ported elsewhere [9,10]. Patients 6 and 7 belong to the kindred described by Ncundorfer and Kuhn [II]; they have not been published previously.…”