What infections cause lupus?

Lupus is an autoimmune disease where the body’s immune system attacks its own healthy cells and tissues. It is not fully understood what causes lupus, but it is believed that both genetic and environmental factors play a role. Some infections have been linked to lupus, either by triggering the onset of the disease in genetically predisposed individuals or by exacerbating symptoms in those already diagnosed. This article explores the current evidence on infections that may be involved in lupus.

Viral Infections

Some research suggests viral infections could contribute to lupus development or flares. Viruses are thought to act as environmental triggers in genetically susceptible individuals. Potential mechanisms include molecular mimicry, where viral proteins are similar to self-proteins, causing the immune system to mistakenly attack body tissues. Viral infections may also cause generalized immune system activation that leads to autoimmunity.

Epstein-Barr Virus

Epstein-Barr virus (EBV) is a common herpesvirus that causes infectious mononucleosis (“mono”). EBV has been closely linked to lupus. People with lupus almost universally have antibodies to EBV, indicating past infection. EBV DNA has also been found in the tissues of lupus patients.

EBV is hypothesized to trigger lupus through molecular mimicry. EBV nuclear antigen 1 (EBNA-1) is similar in structure to a common autoantigen targeted in lupus called Ro. Antibodies formed against EBNA-1 may cross-react with Ro, initiating an autoimmune reaction. EBV infection may also promote generalized B cell activation, increasing autoantibody production.

Other Viruses

Other viruses that have been associated with lupus include:

  • Cytomegalovirus (CMV): Another herpesvirus that may stimulate autoimmunity through molecular mimicry. CMV antibodies are commonly detected in lupus patients.
  • Parvovirus B19: Can cause a lupus-like illness. Linked to production of autoantibodies and flare-ups in established lupus.
  • Hepatitis C virus (HCV): Associated with autoantibody formation in chronic HCV infection. May increase lupus risk.
  • HIV: Can trigger lupus onset and flares. Thought to involve generalized immune activation.
  • Human T-lymphotropic virus type 1 (HTLV-1): Retrovirus that causes immune dysregulation. Implicated in lupus among carriers.

While these viruses may contribute to lupus pathogenesis for some patients, more research is needed to establish definitive causal relationships.

Bacterial Infections

Bacterial infections are less studied than viruses in lupus, but some bacteria may play a role. Proposed mechanisms include molecular mimicry between bacterial and self-antigens, nonspecific activation of the immune system, and direct effects of bacterial products on immune cells.

Streptococcal Infections

Infections with streptococcal bacteria, especially Streptococcus pyogenes, have been associated with lupus. S. pyogenes causes strep throat, impetigo, and other infections. Several observations link strep infections to lupus:

  • Antibodies to S. pyogenes are greater in lupus patients compared to controls.
  • Some lupus autoantibodies cross-react with S. pyogenes antigens.
  • Exposure to S. pyogenes can precede lupus onset, with molecular mimicry as the proposed trigger.
  • Lupus flares have been reported following strep throat.

However, a direct causative role for S. pyogenes remains unproven. Not all lupus patients have a history of streptococcal infections prior to disease onset.

Other Bacteria

Other bacteria less consistently linked to lupus include:

  • Staphylococcus aureus: May stimulate autoantibody production through nonspecific B cell activation.
  • Mycobacteria: Shared antigenic targets with lupus autoantigens could lead to molecular mimicry.
  • Propionibacterium acnes: Antibodies suggest association with lupus, but mechanism is unclear.
  • Helicobacter pylori: Conflicting reports on association with lupus. Any role in pathogenesis is uncertain.

Overall, there is currently limited evidence that specific bacterial infections cause or trigger lupus. More research is warranted.

Fungal Infections

Compared to bacterial and viral infections, there has been little investigation of fungal infections potentially contributing to lupus pathogenesis. One possible mechanism is molecular mimicry between fungal proteins and lupus autoantigens.

A few case reports describe lupus being diagnosed after fungal infections, including with Candida albicans and Cryptococcus neoformans. Patients showed antibodies cross-reacting between the fungi and their own cells. However, these reports are rare, and fungal infections are not an established cause of lupus onset or flares.

Parasitic Infections

A role for parasitic infections in lupus has scarcely been explored. One case report documents a parasite called schistosomiasis apparently triggering lupus onset through molecular mimicry. The patient’s antibodies reacted to both schistosome antigens and their own collagen. After antischistosomal treatment, their lupus symptoms resolved.

Another case report found antibodies against Plasmodium falciparum (the parasite causing malaria) cross-reacted with lupus autoantigens and exacerbated disease activity. However, clear evidence linking parasitic infections to lupus is lacking.

Mechanisms of Infection-Induced Lupus

While numerous infections have been hypothesized to contribute to lupus onset or flares, the mechanistic links are not fully proven. Proposed mechanisms include:

Molecular Mimicry

Molecular mimicry occurs when a foreign antigen resembles self-antigens in structure or sequence. Antibodies formed against the pathogen cross-react with host tissues, causing autoimmunity. This scenario has been described for several viruses, bacteria, fungi, and parasites linked to lupus, but definitive evidence is limited.

Generalized Immune Activation

Infections can cause widespread activation of the immune system, including increased B cell activity and autoantibody production. This nonspecific effect may contribute to lupus onset or flares with various types of infections.

Altered Apoptosis

Some infections impair normal cell apoptosis (programmed cell death), causing excess release of autoantigens. Uncleared apoptotic debris may spark autoimmunity in lupus. Viruses like EBV encode proteins that inhibit apoptosis.

Cytokine Effects

Infections induce cytokine release. Certain cytokines promote inflammatory responses that may exacerbate lupus. Interferon-alpha, in particular, is linked to lupus autoimmunity and is induced by some viruses.

TLR Activation

Toll-like receptors (TLRs) recognize pathogen components. TLR activation can stimulate autoantibody production by immune cells. Some infections may trigger lupus through TLR signaling.

Bystander Activation

In bystander activation, an infection non-specifically stimulates autoimmune T or B cells that target unrelated host antigens, potentially promoting lupus activity.

Do Infections Cause Lupus Flares?

Even if they do not directly cause lupus onset, infections are an established trigger of disease flares and increased activity in lupus patients. Possible reasons include:

  • Increased autoantibody production
  • Immune complex formation
  • Cytokine release stimulating inflammation
  • TLR activation by pathogens
  • Stress effects on the immune system

Many lupus patients report flares during or after viral respiratory infections, sinus infections, urinary tract infections (UTIs), strep infections, and other common illnesses. Disease monitoring during infections is advised.

Risk Factors for Infection-Induced Flares

Some lupus patients have increased susceptibility to infection-provoked flares. Risk factors include:

  • High disease activity level
  • Organ damage from ongoing lupus
  • Immunosuppressant medications
  • Corticosteroid usage
  • Older age
  • Comorbid health conditions

Prompt identification and treatment of infections may help reduce complications in high-risk patients.

Preventing Infection-Triggered Flares

Strategies to prevent flares provoked by infections include:

  • Avoiding contact with sick individuals when possible
  • Practicing good hygiene to reduce pathogen spread
  • Staying up-to-date on immunizations, including influenza and pneumonia vaccines
  • Seeking medical care quickly for suspected infections before they worsen
  • Completing prescribed courses of antibiotics to fully treat infections
  • Monitoring lupus symptoms closely when ill
  • Discussing flare management with the healthcare team


Infections likely contribute to lupus onset or flares in at least a subset of patients. Proposed triggers include viruses like EBV, streptococcal and other bacterial infections, and some fungal and parasitic infections. However, definitively proving these infectious agents directly cause lupus has been challenging. While infections may provoke disease activity, careful precautions and prompt treatment can help reduce complications.

Ongoing research is working to better define links between infections and lupus, with the goal of improving prevention, monitoring, and treatment strategies. A clearer understanding of infection-induced lupus mechanisms could open doors to new therapeutic approaches targeting those pathways.

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