Epstein-Barr virus (EBV) is a human herpes virus that infects approximately 95% of the world’s population. It primarily infects B-lymphocytes and can cause a range of clinical manifestations, including infectious mononucleosis, chronic active EBV infection, and malignancies such as Burkitt’s lymphoma, Hodgkin’s disease, and nasopharyngeal carcinoma. In addition to these well-known associations, EBV infection has also been linked to kidney diseases. In this blog, we will discuss the effects of EBV infection on the kidneys and the mechanisms involved.
By Majd Isreb, MD, FACP, FASN, IFMCP
Effects of EBV infection on the kidneys
EBV, also known as human herpesvirus 4, infects up to 95% of the population, primarily in childhood, then establishes a lifelong latent infection in memory B cells. EBV infection has been recently implicated in the development of several autoimmune diseases, including multiple sclerosis, lupus, rheumatoid arthritis, Sjögren’s syndrome, and autoimmune thyroid diseases.
In the kidneys, Epstein-Barr virus (EBV) infection has been associated with several kidney diseases, including acute interstitial nephritis (AIN), membranous nephropathy, minimal change disease (MCD), and more rarely, focal segmental glomerulosclerosis (FSGS).
EBV and acute interstitial nephritis (AIN)
Acute interstitial nephritis (AIN) is an inflammatory disease that affects the interstitial tissue of the kidneys, which surrounds the tubules. AIN is a rare complication of EBV infection but has been reported in some cases. The exact mechanisms by which EBV infection causes AIN are not fully understood. Still, it is thought that the immune response to EBV infection may trigger an inflammatory response in the kidneys, leading to tissue damage and inflammation.
EBV and IgA nephropathy
In addition to AIN, EBV infection has also been implicated in developing other renal diseases, such as IgA nephropathy and membranous nephropathy. For example, in IgA nephropathy patients, EBV infection has been found to trigger the production of aberrantly glycosylated IgA1. This was not the case in healthy controls. This supports the hypothesis that these patients have a predisposition (genetic or otherwise) to form these aberrantly glycosylated IgA1.
In essence, IgA nephropathy patients tend to form abnormal IgAs, then a trigger such as EBV can induce the mass formation of these abnormal IgAs. These abnormal IgAs then cause an immune response in which the body forms antibodies against these abnormal proteins. The resultant immune complexes then deposit in the glomeruli, leading to glomerulonephritis. Furthermore, EBV has been thought to be the reason behind the racial distribution of IgA nephropathy.
EBV and membranous nephropathy
Membranous nephropathy is a glomerular disease affecting the kidneys’ filtering units, the glomeruli. EBV infection has been associated with the development of membranous nephropathy in some cases. In membranous nephropathy, EBV infection is thought to cause the formation of antibodies that cross-react with a major podocyte protein causing it to be lost in the urine. This will cause significant dysfunction in the glomerular wall filtration system (slit diaphragm) and loss of a massive amount of protein in the urine.
EBV in minimal change disease and FSGS
Minimal change disease (MCD) is another glomerular disease that affects the podocytes in the glomeruli. In some cases, EBV infection has been linked to the development of MCD, although the exact mechanisms are not fully understood. It is thought that EBV infection may trigger an autoimmune response that damages the podocytes and leads to the development of MCD.
Primary Focal segmental glomerulosclerosis (FSGS) is another autoimmune kidney disease. EBV infection has rarely been implicated in the development of FSGS, but the evidence linking EBV to FSGS is limited. The exact mechanisms by which EBV infection may lead to the development of FSGS are not fully understood.
EBV-associated nephropathy
EBV-associated nephropathy (EBVAN) is a rare but potentially life-threatening complication of EBV infection that primarily affects immunocompromised individuals, such as transplant recipients and patients with AIDS. EBVAN is characterized by the presence of large atypical lymphoid cells in the renal tubules and interstitium, which can cause tubulointerstitial nephritis, interstitial fibrosis, and, eventually, kidney failure.
The exact mechanisms of EBVAN pathogenesis have yet to be fully understood. Still, it is thought to involve direct infection of renal epithelial cells by the virus and the subsequent activation of immune responses against infected cells.
Mechanism of EBV-associated kidney diseases
If EBV infects 95% of the population, why do some people develop autoimmune diseases related to EBV while others do not?
While it is true that up to 95% of the population has been infected with Epstein-Barr virus (EBV) at some point in their lives, not everyone who is infected with EBV will go on to develop autoimmune diseases related to EBV. Also, not every case of the autoimmune kidney disease mentioned above is associated with EBV.
The development of autoimmune diseases is a complex process involving genetic, environmental, and immunological factors. One proposed mechanism for developing autoimmune diseases related to EBV is molecular mimicry. Due to structural similarities between EBV antigens and self-antigens, the immune system mistakenly identifies self-antigens as foreign antigens. This can lead to an autoimmune response against self-tissues, resulting in tissue damage and inflammation.
Another proposed mechanism is that EBV infection may dysregulate the immune system, leading to a breakdown in self-tolerance and the development of autoimmune diseases. For example, EBV infection has been shown to activate B and T cells, producing autoantibodies and activating autoreactive T cells.
However, the development of autoimmune diseases is likely to be multifactorial and involve a combination of genetic and environmental factors. While EBV infection may contribute to the development of autoimmune diseases in some individuals, other factors, such as genetic predisposition, environmental triggers, and other infections, may also play a role.
Testing for EBV
Epstein-Barr virus (EBV) infection can be diagnosed using various laboratory tests, including serological tests, molecular tests, and viral culture.
Serological tests detect antibodies to EBV in the blood. These tests can determine whether an individual has been infected with EBV in the past or is currently infected. Two main types of antibodies can be detected: IgM and IgG. IgM antibodies are produced early in the course of infection, while IgG antibodies are produced later and persist for life. Therefore, a positive IgM test indicates acute infection, while a positive IgG test indicates previous or current infection.
Antibodies to the viral capsid antigen (VCA) appear early in EBV infection and peak between 2-4 weeks after the appearance of infectious mononucleosis. In comparison, early antigen IgG antibodies (EA-D IgG) are usually associated with the acute stage of EBV infection. Finally, EB nuclear antigen IgG antibodies are conventionally thought to indicate prior exposure to EBV. Therefore, we recommend using a panel of all these antibodies when testing a patient for latent or active EBV. The following table will help you interpret these results:
| VCA-IgM | VCA-IgG | EA-D, IgG | EBNA IgG | Likely interpretation |
| Negative | Negative | Negative | Negative | No EBV infection |
| Positive | Positive | Negative | Negative | Early primary infection |
| Negative or positive | Positive | Positive | Negative | Active infection |
| Negative | Positive | Negative | Positive | Prior infection |
| Negative | Positive | Positive | Positive | May indicate reactivation |
Molecular tests detect the presence of EBV DNA in the blood or other body fluids, such as saliva or cerebrospinal fluid. Polymerase chain reaction (PCR) is the most commonly used molecular test for the detection of EBV DNA. However, unfortunately, PCR can detect latent EBV in as low as 54% and as high as 94% of seropositive individuals, according to the tests above. In addition, it has poor sensitivity and specificity even in primary EBV infection.
Viral culture involves the isolation and growth of the virus from a sample, such as blood or saliva. However, viral culture is rarely used to diagnose EBV infection due to its low sensitivity and the time required for the virus to grow.
How to treat EBV or chronic EBV infections
There is no specific treatment for EBV infection or chronic latent EBV infections.
Treatment for chronic latent EBV infections may involve a combination of antiviral medications, immunomodulatory drugs, and supportive care. However, there is no consensus on the optimal treatment approach, and the treatment plan should be individualized based on the patient’s symptoms and clinical presentation.
Antiviral medications, such as acyclovir, valganciclovir, and ganciclovir, may suppress EBV replication and reduce the viral load. However, these medications have limited efficacy against EBV.
Immunomodulatory drugs, such as corticosteroids, rituximab, and interferon, may modulate the immune response and reduce inflammation. These drugs have been shown to be effective in some patients with chronic EBV infections, but their use is associated with potential side effects and should be carefully monitored.
Supportive care, such as rest, hydration, and a healthy diet, can also help to manage symptoms and promote recovery in patients with chronic EBV infections. However, it is essential to note that managing chronic latent EBV infections is complex and requires a multidisciplinary approach.
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Is there a natural treatment for EBV?
Several natural treatments may help manage EBV infection symptoms, although limited scientific evidence supports their effectiveness. These include:
- Rest and stress reduction: Rest and stress reduction can help to boost the immune system and promote healing. Getting adequate sleep, practicing relaxation techniques, such as meditation or yoga, and avoiding stressors can be helpful.
- Balanced diet: Eating a balanced diet rich in fruits, vegetables, whole grains, and lean proteins can help to support the immune system and reduce inflammation.
- Herbal remedies: Certain herbs, such as echinacea, elderberry, and astragalus, have been traditionally used to boost the immune system and may help manage EBV infection.
- Probiotics: Probiotics, which are beneficial bacteria that live in the gut, may help to support the immune system and reduce inflammation. Consuming probiotic-rich foods, such as yogurt or kefir, or a probiotic supplement may be helpful.
- Vitamin and mineral supplements: Certain vitamins and minerals, such as vitamin C, vitamin D, zinc, and selenium, are essential for immune function and may help manage EBV infection. However, consulting with an Integrative healthcare provider before taking any supplements is important.
It is important to note that natural treatments should not be used as a substitute for a comprehensive integrative approach. Additionally, it is essential to consult with an integrative healthcare provider before starting any natural treatment, as some natural treatments may interact with medications or have potential side effects.
The bottom line
EBV is a highly prevalent virus affecting approximately 95% of the world’s population. It primarily infects B-lymphocytes, making them immortal. EBV has been linked to many autoimmune diseases. For example, it has been linked to autoimmune kidney diseases such as IgA nephropathy, membranous nephropathy, minimal change disease, and FSGS. Testing these patients for latent EBV infection is, therefore, important.
