Immunoglobulin M: The First Responder in Infectious Disease Diagnosis

Proteins exert their effects primarily by recognizing and binding to other molecules, a process that relies on the compatibility of their shapes. This principle is illustrated by the interaction between antibody proteins and antigens, as well as the binding of morphine or heroin to opioid receptor proteins.

Proteins are structured at three, and occasionally four, distinct levels. The primary structure consists of a linear chain of amino acids. The secondary structure involves the folding or coiling of this chain. The tertiary structure represents the overall three-dimensional shape of a folded protein, while the quaternary structure occurs when two or more peptide chains come together to form a larger protein complex. For proteins to function biologically, they must be folded into these specific three-dimensional shapes.

Beginning in the mid-1950s, American biochemist Christian Anfinsen, working at the National Institutes of Health, explored the relationship between protein structure and function. He focused on ribonuclease, an enzyme responsible for breaking down ribonucleic acid (RNA), due to its stability, small size, extensive study, and availability in purified form. In 1957, Anfinsen discovered that when ribonuclease's three-dimensional structure was disrupted, causing it to lose its biological activity, it could spontaneously refold back into its native, fully functional shape, thereby restoring its enzymatic activity. This behavior was observed in many other proteins as well.

From these experiments, Anfinsen concluded that the information necessary for a protein to achieve its final three-dimensional conformation is encoded in its primary structure—specifically, its amino acid sequence. He proposed the "thermodynamic hypothesis," suggesting that ribonuclease adopts its three-dimensional structure because it is the most stable configuration. In recognition of his groundbreaking work linking amino acid sequences to the biologically active shapes of proteins, Anfinsen was awarded the Nobel Prize in Chemistry in 1972.

Several diseases, including Alzheimer’s, Parkinson’s, and Huntington’s, have been linked to the accumulation of misfolded proteins. These misfolded proteins are thought to originate from amyloid proteins and are believed to increase with age, potentially influenced by genetic factors.

Immunoglobulin M (IgM), the largest antibody present in the human circulatory system, is the first to respond during an infection. Its presence is frequently utilized as a key indicator in the diagnosis of infectious diseases.