Autoantibodies and Antibodies: Understanding Their Roles and Implications

Functional Autoantibodies (AABs) in Acute SARS-CoV-2 Infection

A recent study delves into the role of functional autoantibodies (AABs) in acute SARS-CoV-2 infection. It reveals that even mild cases of COVID-19 can trigger the generation of diverse and functional AABs. Persistently elevated autoantibodies have been observed in individuals suffering from long COVID (LC). By employing a comprehensive human protein array consisting of over 21,000 proteins, researchers identified diverse AAB targets in LC patients. These targets correlated with the patients' symptoms, particularly those affecting the nervous system. Elevated AABs against nervous system proteins were prevalent in LC patients exhibiting neurocognitive and neurological symptoms.

In one part of the study, purified Immunoglobulin G (IgG) samples from these individuals were tested and found to react with human pons tissue. They also cross-reacted with mouse sciatic nerves, spinal cord, and meninges. Notably, antibody reactivity to sciatic nerves and meninges was linked to patient-reported headaches and disorientation. When IgG from patients was passively transferred to mice, it led to increased sensitivity and pain, mirroring the symptoms reported by the patients. Similarly, mice injected with these IgG samples experienced loss of balance and coordination, reflecting the dizziness reported by the donors. These findings suggest that targeting AABs could be beneficial for some LC patients.

Sources:

1. A causal link between autoantibodies and neurological symptoms in long COVID
2. Woodruff, M.C., Ramonell, R.P., Lee, F.E., & Sanz, I. (2020). Broadly-targeted autoreactivity is common in severe SARS-CoV-2 Infection. medRxiv. doi:10.1101/2020.10.21.20216192

The Functional Role of Antibodies

Antibodies are proteins produced by the immune system to protect the body against unwanted substances, such as pathogens. When an unwanted substance, known as an antigen, enters the body, antibodies bind to it, neutralizing or eliminating it from the system.

Common Autoantibody Tests

Here are the five most common autoantibody tests, along with their acronyms:

1. Islet Cell Cytoplasmic Autoantibodies (ICA)
2. Glutamic Acid Decarboxylase Autoantibodies (GADA)
3. Insulinoma-Associated-2 Autoantibodies (IA-2A)
4. Insulin Autoantibodies (IAA)
5. Zinc Transporter-8 Autoantibodies (ZnT8A)

Functions of Autoantibodies

Natural autoantibodies are primarily of the IgM type, encoded by unmutated V(D)J genes, and display moderate affinity for self-antigens. They provide a first line of defense against infections, likely serve housekeeping functions, and contribute to the homeostasis of the immune system.

Sources:

1. Elkon, K., & Casali, P. (2008). Nature and functions of autoantibodies. Nature Clinical Practice Rheumatology, 4(9), 491-498.
2. Shoenfeld, Y., & Isenberg, D.A. (1989). Natural autoantibodies. Annals of the New York Academy of Sciences, 650, 425-433.

Examples of Detectable Autoantibodies

Three common autoantibodies that can be detected include:

1. Rheumatoid Factor (RF): An autoantibody targeting the Fc portion of IgG, frequently found in rheumatoid arthritis.
2. Anti-Nuclear Antibodies (ANAs): Commonly found in systemic lupus erythematosus (SLE).
3. Anti-Citrullinated Protein Antibodies (ACPAs): Often detected in rheumatoid arthritis.

Sources:

1. Tan, E.M., Feltkamp, T.E.W., Smolen, J.S., Butcher, B., Dawkins, R., Fritzler, M.J., ... & Koike, T. (1997). Range of antinuclear antibodies in "healthy" individuals. Arthritis & Rheumatism, 40(9), 1601-1611.
2. van Venrooij, W.J., van Beers, J.J., & Pruijn, G.J. (2011). Anti-CCP antibodies: the past, the present and the future. Nature Reviews Rheumatology, 7(7), 391-398.

Autoantibodies vs. Antibodies

Autoantibodies are misguided or pathogenic antibodies that react to the body's own proteins, potentially leading to abnormal immune responses that attack the body's cells, tissues, and organs. This contributes to the development of autoantibody diseases.

Antibodies, on the other hand, are proteins produced by the immune system to target and eliminate foreign substances (antigens) from the body.

Sources:

1. Meroni, P.L., & Schur, P.H. (2010). ANA screening: an old test with new recommendations. Annals of the Rheumatic Diseases, 69(8), 1420-1422.
2. Plotz, P.H. (2003). The autoantibody repertoire: searching for order. Nature Reviews Immunology, 3(1), 73-78.

Autoantibodies and JNJ's Nipocalimab

Nipocalimab, a drug developed by Johnson & Johnson (J&J), has shown clinical efficacy across four diseases caused by autoantibodies. These autoantibodies, as a type of immune system foot soldier, mistakenly attack the body's own proteins, leading to various autoimmune conditions. Nipocalimab represents a promising therapeutic approach in managing these diseases.

Sources:

1. J&J News Release (2023). J&J's Nipocalimab shows promise in treating autoantibody diseases. Retrieved from J&J Website
2. Smith, R.J., & Alexander, S.D. (2022). Clinical efficacy of nipocalimab in autoantibody-mediated diseases. Journal of Clinical Immunology, 42(5), 895-907.

Understanding the role of autoantibodies and antibodies is crucial for diagnosing and treating autoimmune diseases and conditions like long COVID, where autoantibodies play a significant role in symptom manifestation and progression.

Note: By reading my blog, you acknowledge that I do not provide medical diagnoses or treatments. The information provided is meant to answer frequently asked questions and is gathered from reputable scientific papers.