There are a number of Conditions and Autoimmune Diseases strongly associated with EBV reactivation and latent infection, please focus on what is relevant to you, which has been detailed comprehensively below.

 

• Chrons Disease

• Ulcerative Colitis

• Hashimoto's Thyroiditis

• Grave’s disease

• Rheumatoid arthritis

• Multiple sclerosis

• Sjögren’s syndrome

• H.Pylori Negative Gastritis

• Systemic lupus erythematosus **

 

[1][8]

 

Chrons Disease 

 

Numerous studies have employed EBER detection for EBV-positive cells in colonic mucosal biopsies from patients with Crohn’s disease. In one study involving 11 individuals, EBER was identified in 63% of cases. Another study reported EBER positivity in the colonic mucosa of 81% of Crohn’s disease patients, though the sample size was not specified." [35]

 

In chrons EBV has been shown to spread beyond B lymphocytes and infect colonic epithelial cells, as demonstrated by the detection of EBV DNA in enterocytes. This direct epithelial infection may contribute to mucosal damage and intensify local inflammation. 

 

Furthermore, EBV interferes with the body’s immune system by producing viral proteins such as LMP1 and EBNA1. These proteins disrupt how infected cells are recognized by the immune system and make the infected cells more resistant to being destroyed. They also increase the production of immune-signaling molecules like IL-10 and TNF-α, which can alter normal immune responses. Altogether, these changes lead to immune system imbalance and may trigger autoimmune-like inflammation in the gut.

 

Compounding this, EBV-driven immune activation has been associated with cytotoxic T-cell (CD8⁺) exhaustion and reduced natural killer (NK) cell activity, impairing the host’s ability to control the virus. This immune exhaustion reinforces persistent infection and chronic inflammation, both of which are key features in the progression of Crohn’s disease.[35]

 

Ulcerative Colitis

 

A study of 92 individuals with ulcerative colitis found that approximately 39% had Epstein–Barr virus (EBV) present in their colonic mucosa. The number of EBV-infected cells was significantly associated with more severe disease, marked by increased inflammation, ulcer development, and a higher likelihood of hospitalisation.

 

This association appears to be driven by EBV reactivation within B lymphocytes in the intestinal tissue. The detection of BZLF1, a gene indicating transition to the lytic phase, suggests that the virus had shifted from latency to active replication. This reactivation likely exacerbates mucosal inflammation and contributes to tissue damage and ulceration in affected patients [34].

 

Hashimoto's Thyroiditis

 

EBER expression is a strong marker of latent EBV infection, and is detected in 80.7% of Hashimoto's thyroiditis cases. Additionally, cytoplasmic expression of LMP1, an EBV latent membrane protein was observed in 34.5% of cases These findings suggest a high prevalence of latent EBV presence in Hashimoto's thyroid tissue [9].

 

One study examined EBV-related antibodies in 60 patients with Hashimoto’s thyroiditis (HT), and 60 healthy individuals. Researchers specifically measured four EBV antibodies in the blood: 

 

• VCA IgM, linked to recent or acute EBV infection

• VCA IgG, linked to past EBV infection

• EBNA-1 IgG, linked to past infection and lifelong viral latency

• EA IgG, associated with EBV reactivation

 

All participants had positive VCA IgG and EBNA-1 IgG, indicating past EBV exposure. However, about one-third of HT patients showed significantly higher levels of EA IgG, compared to only a few in the control group. Since EA IgG is a marker of reactivation, not acute infection, this suggests that EBV reactivation, rather than simple past exposure, may be involved in the initiation or perpetuation of Hashimoto’s thyroiditis.

 

In Hashimoto’s  patients with underactive thyroid function, higher levels of EBNA-1 IgG, a marker of latent viral presence, were inversely correlated with low T3 levels, suggesting that the greater the viral activity or immune response to EBV, the lower the thyroid hormone production.

 

Additionally, among healthy individuals, higher EBNA-1 IgG levels correlated with elevated anti-TPO antibodies, a key marker of thyroid autoimmunity. This indicates that EBV exposure may initiate autoimmune responses even before clinical disease appears.[31]

 

Graves Disease

 

EBV, which remains latent in B lymphocytes, has been detected in the thyroid tissue of 62.5% of Graves’ disease cases through the presence of EBV-encoded RNA (EBER), a marker of latent infection. 

 

Mechanistically in Graves’ disease, the excessive production of thyrotropin receptor antibodies (TRAb) overstimulates the thyroid gland, leading to hyperthyroidism. Given EBV’s ability to persist and periodically reactivate, researchers investigated its potential role in influencing these TRAb levels. 

 

Their findings demonstrated that TRAb levels were moderately but significantly correlated with EBV EA antibody levels, a marker of viral reactivation. This association suggests that EBV reactivation may stimulate B cells predisposed to produce TRAb, thereby amplifying the autoimmune response and potentially worsening the clinical severity of Graves’ disease. [9][31]

 

Rheumatoid Arthritis (RA)

 

Patients with rheumatoid arthritis (RA) consistently exhibit elevated antibodies against multiple Epstein–Barr virus  proteins, including EBNA-1, EBNA-2, VCA, and EA. In addition, EBV DNA levels are approximately ten times higher in RA patients compared to healthy controls, suggesting persistent or reactivated viral infection. Notably, EBV DNA and transcripts have also been detected at significantly higher levels within the synovial tissue of RA patients, implicating local viral activity in the inflamed joints.

 

Evidence further indicates impaired cellular immune control of EBV in RA. Where CD8⁺ T cells, which normally suppress EBV-infected B cells are often dysfunctional or exhibit features of exhaustion. 

 

Compounding this, EBV antigens such as EBNA-1 share sequence homology with human proteins expressed in joint tissues. This molecular mimicry may misdirect the immune response and contribute to the breakdown of self-tolerance, promoting autoimmunity and joint inflammation characteristic of RA [11].

 

Furthermore a study of 133 RA patients over six months demonstrated that as their RA symptoms improved, EBV antibody levels dropped. Across all patients, lower levels of long-term EBV antibodies (anti-EBNA1-IgG) were linked to remission. [10]

 

Multiple Sclerosis 

 

EBV has emerged as a key environmental factor in the development of multiple sclerosis (MS), with strong epidemiological and immunological evidence linking the two. Over 99% of individuals with MS are EBV-positive and MS is virtually unheard of in EBV-seronegative individuals. 

 

Large cohort studies have shown that the risk of MS increases 32-fold following EBV infection. Importantly, MS typically develops months to years after EBV infection, indicating that it is not caused by the acute phase but rather by long-term immune dysregulation.

 

Several mechanisms have been proposed to explain how EBV may trigger or sustain MS. One is EBV’s ability to infect and transform B cells, allowing autoreactive B cells that would normally undergo cellular death to survive and produce antibodies targeting self-antigens. These EBV-infected B cells can migrate to the central nervous system, where they may drive local inflammation and tissue damage. 

 

Furthermore, people with MS exhibit elevated defences against EBNA1, particularly  CD4+ T cells, which coordinate the immune response. In people with MS, these CD4+ T cells react to EBNA1, but then can also mistakenly react to myelin, the protective coating around nerves. This is because parts of EBNA1 look similar to parts of myelin, a phenomenon called molecular mimicry.

 

Genetic factors, such as the HLA-DRB1*15:01 allele, the strongest genetic risk factor for 

MS also interacts with EBV exposure to increase disease risk. This allele is associated with elevated anti-EBNA1 antibody levels and altered T-cell responses. 

 

Overall, EBV appears to be a necessary factor in MS pathogenesis. Its ability to manipulate B-cell survival, provoke cross-reactive immune responses, and alter antigen presentation likely contributes to the autoimmune processes seen in MS. [12][33]

 

Sjorgens Syndrome (SjS)

 

Presence of EBV DNA and proteins was found in the salivary glands of approximately 50% of participants in 2 studies involving 8 and 7 patients with Sjorgrens Syndrome, compared to only 8% of healthy controls. [36][37] 

 

Research is limited, but one study found that people with SjS are more likely to show signs of recent EBV reactivation compared to healthy individuals, by way of increased numbers of early-stage B-cells. In addition, there was a higher presence of specialized helper T-cells, which support B-cell growth and antibody production. This increased activity may contribute to a stronger and more harmful immune attack on the body’s own glands.

 

Researchers concluded that EBV may drive the immune system into overdrive in SjS, causing both B-cells and T-cells to become overly active. This heightened immune response, especially in the glands, could explain the chronic tissue damage and inflammation commonly seen.

 

H.Pylori Negative Gastritis

 

In a cohort study involving 119 patients with gastritis who tested negative for Helicobacter pylori, EBV-infected gastric epithelial cells were identified in 14 cases. [39] Although the overall prevalence was relatively low, EBV infection should be considered as a potential etiological factor in cases of persistent, H. pylori-negative gastritis.

 

Chronic Fatigue

 

EBV is one of the most studied infectious triggers for CFS. After EBV infection, the immune system becomes highly active, and in some people, this immune activation doesn't shut off. EBV may “set the stage” for CFS, but not everyone exposed to EBV develops fatigue; it's a combination of biology, psychology, and behavior.

 

One study tracked 200 teenagers who had acute EBV infection and followed them for six months to see who developed lasting fatigue. At six months after infection 91 out of 195 (47%) still reported significant fatigue, and 14% met criteria for CFS. The study simultaneously discovered that fatigue wasn’t mainly predicted by only viral or immune measures like viral load alone. Rather, psychological and physical functioning at the time of illness are key risk factors, such as:

 

• High anxiety levels at the time of infection

• Lower physical activity 

• Higher non EBV related inflammation

• Lower vitamin B12 levels [38]