To define the proteomic profile of sporadic late-onset nemaline myopathy (SLONM) and explore its pathogenesis.

SLONM is characterized by accumulation of nemaline rods in muscles without any significant inflammation. It is commonly associated with a monoclonal protein (MP) and responds to treatment with intravenous immunoglobulins or autologous stem-cell transplantation. However, underlying disease mechanisms remain unknown.

We performed label-free liquid chromatography mass spectrometry on laser-dissected frozen muscle samples from 5 patients with SLONM, 3 with an associated monoclonal protein (MP), and 4 controls, to determine the proteomic profile, focusing on immune-related proteins and the immunoglobulin light chain variable regions. 

294 proteins were differentially expressed, 272 upregulated and 22 downregulated. Among the top 100 upregulated proteins, the most common categories were as follows: nuclear/nucleic acid metabolism (24%), extracellular matrix/basal lamina (17%), immune response (13%), and actin dynamics (8%). Downregulated proteins consisted mostly of contractile proteins. Among all upregulated proteins, there were 65 related to the immune system, including 8 proteins involved in MHC1 complex and antigen processing, 15 in MHCII complex and phagocytosis, and 23 in B and/or T cell function. Among 9 upregulated immunoglobulin proteins, there were 2 light chain variable region genes. However, these were also detected in SLONM cases without an MP, and there was no evidence of clonally-dominant immunoglobulin deposition in SLONM-MP.  Increased MHC1 reactivity was present in fibers containing nemaline rods as well as adjacent non-atrophic fibers.