Anomalous Peaks Observed in the Mass Spectrometry of Light Chains Correlate with the Diagnosis of AL Amyloidosis

Background: Systemic light chain (AL) amyloidosis is a disease characterized by the misfolding of monoclonal immunoglobulin light chains into amyloid proteins. These misfolded proteins deposit in tissues and organs, causing structural damage and organ dysfunction. Pathological biopsy is the gold standard for diagnosing AL. Mass spectrometry, as a recently developed method for detecting light chains, is increasingly being utilized to assist in the diagnosis of plasma cell disorders. Method: Matrix-Assisted Laser Desorption Ionization time-of-flight (MALDI-TOF) is used to detect λ and κ light chains in the peripheral blood of patients. This method identifies λ and κ light chains based on the differences in their mass-to-charge ratios. Result: In patients suspected of having plasma cell disorders, we utilized MALDI-TOF to detect light chains in their peripheral blood. We observed that the presence of abnormal peaks in the mass spectrum is often associated with a diagnosis of amyloidosis. Among the 56 individuals tested, 9 exhibited abnormal peaks in the light chain profiles: 5 with amyloidosis, 3 with multiple myeloma (MM), and 1 with monoclonal gammopathy of undetermined significance (MGUS). Of these 56 individuals, 6 were diagnosed with AL based on pathological findings, and 5 of them showed abnormal peaks in peripheral blood light chain mass spectrum. Therefore, based on our estimation with a limited sample size, using pathological diagnosis as the gold standard, the sensitivity of diagnosing amyloidosis through MALDI-TOF detection of light chain abnormal peaks is 83.3%, and the specificity is 92.2%. However, due to our limited sample size, the sensitivity and specificity values require validation through testing with a larger sample size. The specific significance of the differential peak has not been thoroughly investigated. Based on published literature and the positions of the peaks, it is hypothesized that this may be associated with glycosylation of light chains, which could result in an abnormal protein structure. We intend to further investigate this in our future research. Conclusion and significance: The diagnosis of AL amyloidosis primarily depends on pathological assessment via tissue biopsy. Our research indicates that the detection of abnormal peaks in peripheral blood using MALDI-TOF for light chains demonstrates good sensitivity and accuracy for the diagnosis of AL amyloidosis. Although the sample size remains relatively small, our findings offer potential insights and approaches for developing non-invasive diagnostic methods for amyloidosis.