Herein, we report an exceptional case of IgA–kappa-type LHCDD accompanied by focal amyloid deposition. Cases of MIDD with amyloid deposition have been reported, but the details of these cases were not elucidated [3] [5] [6]. Furthermore, MS was not primarily used to diagnose these cases. Therefore, this is the first case of LHCDD with focal amyloid deposition that was diagnosed through MS analysis of glomerular deposits.
Several factors in the present case suggest non-amyloid-like features of the deposits.
First, the deposits were only slightly Congophilic. As the birefringence was initially too weak to be observed, higher magnification was required, revealing faint birefringence under polarised light. However, the intensity of the birefringence appears to be weaker than those in previous cases [3][7]. Birefringence occurs because of the unique three-dimensional structure of amyloid fibrils. The glomerular deposits in our case showed faint birefringence mainly in the periphery, in contrast to the previous cases wherein birefringence was mostly observed in the mesangial and capillary deposits. The accumulation of numerous light chains in the glomeruli may not have formed the three-dimensional structure of amyloids.
Furthermore, these fibrillar deposits may not form typical amyloid fibrils. Based on previous cases of LCDD with fibrillar deposits and negative Congo red staining, our findings suggest that the fibrillar deposits originated from immunoglobulin light-chain fragments but have not formed an amyloid tertiary structure [4][5][6]. A previous case also presented with simultaneous deposition of fibrillar structures and powdery deposits in the glomerulus [8]. Although the sample in the present case was formalin-fixed, not only fibrillar structures but also powdery deposits were suspected under high magnification during electron microscopy.
Second, the deposits were strongly stained with periodic acid-Schiff (PAS) and periodic acid-methenamine silver (PAM). In cases of renal amyloidosis, amyloid deposits are weakly positive with PAS staining; however, argyrophilia is lost due to the expanded mass of amyloid deposits that replace the normal mesangial matrix [7]. In contrast, deposits in cases of MIDD are strongly argyrophilic as they are composed of extracellular matrix proteins, such as type IV collagen, laminin, and proteoglycans containing heparan sulphate, accompanied by light chains [8]. Therefore, strong positivity with PAS and PAM suggests that the deposits in our case were not typical amyloids.
Third, the lambda chain is more amyloidogenic than the kappa chain [8] because of the former’s tertiary structure [9]. In our case, both immunohistochemical staining and MS revealed that the deposits were largely comprised of kappa chains, which may explain why amyloid fibril formation was minimal.
Initially, we assumed our case as having immunoglobulin heavy- and light-chain (AHL) amyloidosis. However, a previous review described the characteristics for the diagnosis of AHL amyloidosis as (i) equal staining on immunofluorescence for both heavy and light chains or (ii) large spectra for both heavy and light chains on LMD/MS [10]. Furthermore, previous cases of AHL amyloidosis had greater deposits of heavy chains than light chains [10][11]. In our case, there was an abundance of light chains, whereas the amount of heavy chains was minima; these features are not consistent with those of AHL amyloidosis. Therefore, we believe that our patient did not have AHL amyloidosis.
Co-deposition of amyloid fibrils and non-amyloid immunoglobulins has been well-described [12][13][14]. Manabe et al. attempted to distinguish amyloidogenic and non-amyloidogenic deposits using MS [15]. They performed amyloid purification followed by MS, revealing co-deposition of immunoglobulin light-chain (AL) amyloid and non-amyloid heavy chains. Their case had deposition of predominantly AL amyloids and simultaneous deposition of non-amyloid monoclonal immunoglobulins. Additionally, they raised a question on the simultaneous development of AL and AH amyloidosis, because of the extremely rare prevalence of AH amyloidosis. As the MS findings in our case were in contrast to those of a previous case [10], we believe that the our case did not have AHL amyloidosis but simultaneous deposition of non-amyloid and amyloid deposits.
In contrast to a case of AL amyloidosis with deposition of non-amyloid monoclonal immunoglobulins [15], our case showed IgA–kappa-type LHCDD with focal amyloid deposition. MS revealed large deposits of the kappa constant region, whereas only small amounts of heavy-chain components were detected. However, simultaneous deposition of heavy chains was observed based on positive IgA immunofluorescence staining. Slight positivity with Congo red staining suggests that most of the kappa chains do not form the unique tertiary structure of amyloids. Therefore, we diagnosed the patient as having IgA–kappa-type LHCDD with focal amyloids. This is a rare case wherein immunoglobulin and amyloid fibril deposition occurred simultaneously. In the future, accumulation of MS data from similar cases may help clarify the mechanisms of amyloid fibrillation.
We reported a case of LHCDD with focal amyloids. MS is an effective tool that can accurately identify the characteristics of glomerular deposits.