Autoimmunity and CP/CPPS

yes-no
Some researchers have theorised that CP/CPPS may be the result of an autoimmune process or a chronic inflammatory process that is maintained in CPPS patients as a result of a breakdown of immunoregulatory mechanisms in the immediate environment of the prostate. Classic autoimmunity is a complex biochemical process in which the body attacks itself. Scientifically:

“Autoimmune diseases are often manifested as organ inflammation with loss of function, and detectable autoreactive T cell and autoantibody responses. In the proper genetic context … these parameters of autoimmunity can result from a single pivotal event: the induction of a strong and persistent T cell response for a foreign or unrelated self peptide that mimics the target self peptide.” Reprod Immunol 1998 Feb, Mechanism of ovarian autoimmunity: induction of T cell and antibody responses by T cell epitope mimicry and epitope spreading. Garza et al

Some of the classic autoimmune diseases are systemic lupus erythematosus (SLE), Crohn’s disease, diabetes, psoriasis, Reiter’s disease, rheumatoid arthritis, glomerulonephritis, rheumatic fever, polymyositis, autoimmune thyroiditis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), myasthenia gravis, scleroderma, and Sjogren’s syndrome. Some other diseases, such as ulcerative colitis and multiple sclerosis, may have autoimmune components. Autoimmunity is a topic of research since much is not understood about this phenomenon. In 2000 new pathways which can lead to autoimmunity were uncovered.

Recently much currency has been given to the concepts of molecular mimicry and bystander activation. It is beyond the scope of this website to explain these complex phenomena other than to say that a one-time event, usually an infection or stressor of some sort, can leave behind a residual inflammation caused by the body’s immune system mistakenly attacking the body’s own tissues.

In researching autoimmunity and pelvic pain syndrome/prostatitis, rodents are used because it’s fairly easy to induce autoimmune prostatitis in rodents by injecting them with cells from their male accessory glands (humans also have male accessory glands).

What can cause autoimmune reactions?

So why would our bodies be attacking our prostates (or nearby urogenital tissues, like urethra, bladder or epididymis)? Researchers have suggested a number of paths which may, in theory, lead to autoimmunity:

Hit-and-Run Infection

There are numerous studies in the scientific literature which prove the role of infection in autoimmunity. Viruses and bacteria are readily implicated. Reiter’s disease can usually (but not always) be traced back to an infection of the genito-urinary tract or bowel. One of the classic symptoms of Reiter’s is chronic prostatitis (as well as joint pain, conjunctivitis and other symptoms).

Apart from viruses and bacteria, parasites and even normal bacterial flora can provoke autoimmune diseases.

It is also possible that a persistent, ongoing infection can cause an autoimmune reaction, but usually no infection can be found. Curing any infection found may make no difference to an established autoimmune response.

Toxic Exposure

We already know that some antibiotics can induce autoimmunity. Then in May 1999 it was reported that researchers had found that chemical exposures can cause genetic reshuffling — activating part of the immune system to cause the symptoms of fatigue, rashes, muscle pain and a litany of other vaguely defined ills.

One component of the immune system allows cells to ”recognize” bacteria, viruses or parasites that have invaded before. These so-called memory cells rearrange their DNA through a cut-and-paste process to match the invaders. It is this ability to cut and paste DNA that some researchers think may get activated after exposure to chemicals. An example is Gulf War veterans, where exposures to environmental (toxins) may have played a role in the pathogenesis of Gulf War Syndrome. Read the abstract for this study.

Physical Trauma

It is well known today that vasectomy can lead to an autoimmune reaction, especially orchitis (inflammation of one or both testicles), because of the possibility of exposing the body’s tissues to sperm via the incisions used during the operation and possible sperm leakage thereafter. Here are studies to support this:

  1. Nippon Hinyokika Gakkai Zasshi 1999 Sep;90(9):763-8 Establishment of murine model of autoimmune male infertility. Sakamoto Y, Matsumoto T, Kumazawa J.
  2. Allerg Immunol (Paris) 1991 Apr;23(4):121-5 Immunological causes of male infertility. Hassoun S, Drouet M, Le Sellin J, Bonneau JC, Sabbah A

Similarly, it may be possible for other tissues in the male urogenital tract to become sensitized to sperm, PSA and other secretions. The “trauma” which allows secretions to get into places they shouldn’t be could result from numerous things such sports injury, operative procedures and even Tantric sex practices (ejaculation suppressed by grasping penis – very unwise).

Note: Some mice can develop autoimmune prostatitis after having their thymus glands removed.

Diet

Diet can play a role in the development of autoimmune diseases. Classic examples are coeliac disease and juvenile diabetes.

Experiments with rodents have also shown that diet can cause autoimmunity. Two groups of mice were raised in germ-free environments, one group given an elemental diet consisting of pure proteins, minerals and vitamins while the other was fed on normal food. The mice eating the normal diet had a far higher incidence of autoimmune disease.

See :J Immunol 1999 Jun 1;162(11):6322-30, The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. Maldonado et al.

Genetic Predisposition

It is accepted now that the tendency to develop autoimmune reactions can run in families. Anecdotally, many men with CPPS have fathers with the disease or family members with other autoimmune diseases. Jordan Dimitrakov, a prostatitis and IC researcher, studied a number of twins who both had pelvic pain conditions. This may suggest autoimmunity. Genetic predisposition has been demonstrated in mice too. For instance, diabetic mice have background genes which favour severe autoimmune manifestations, including prostatitis, irrespective of the target tissue:

  1. J Exp Med 2000 Jan 17;191(2):313-20, Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. Horai et al.
  2. J Autoimmun 1998 Dec;11(6):603-10. Non-obese diabetic (NOD) mice are genetically susceptible to experimental autoimmune prostatitis (EAP). Rivero et al.

Lastly, certain breeds of genetically susceptible mice developed spontaneous autoimmune lesions of the genito-urinary tract even when raised in a germ-free environment.

Stress

The field of psychoneuroimmunology is in its infancy, but several studies have linked the onset and severity of autoimmune diseases to psychological stress. See, for example: Annu Rev Psychol 1996; 47: 113-42 Health psychology: psychologic factors and physical disease from the perspective of human psychoneuroimmunology. Cohen et al.

Studies linking Autoimmunity to CP/CPPS

In 1998, Richard B. Alexander and colleagues found elevated levels of tumor necrosis factor alpha (TNFa) and interleukin-1 beta (IL-ib) in the seminal fluids of men with CPPS. In 1997, Dr. Alexander had showed that T-cells from some men with CPPS reacted to normal prostatic proteins (Urology 1997; 50:893-9). He thought that this may suggest autoimmunity.

More suggestive studies followed:

Some researcher theorized in 2014 that autoimmunity of some sort plays a part in a complex cascade that leads to CPPS. There is still active research in this area, mostly with rodents in which a form of prostatitis is artificially induced.

Treatments

Dr Daniel Shoskes noted in 2000 that one of the only chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients to have achieved a verified, long-term and complete remission is a kidney transplant patient who underwent full immunosuppression (see Palapattu GS, Shoskes DA. Resolution of the chronic pelvic pain syndrome after renal transplantation. J Urol. 2000 Jul;164(1):127). Of course this treatment is not practical for the vast majority of CP/CPPS patients.

It should be noted that this was before the Wise-Anderson protocol emerged, after which many patients report a cure or a 90%+ improvement. Dr Shoskes has his own dissenting view on autoimmunity and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Webmaster’s View

The view of this website is that autoimmunity is unlikely to underlie CPPS because:

  1. Almost all men recover from CPPS using non-drug therapies. True autoimmunity does not just go away.
  2. Autoimmunity causes real organic damage to organisms. This is the case in true autoimmune prostatitis, the rare “granulomatous prostatitis”, a condition characterized by an immune reaction directed against prostate that is associated with the HLA-DRB1*1501 allele. If CPPS were an autoimmune condition, we should see some real prostate organ damage, but we don’t.
  3. The main researcher pushing this theory, Richard Alexander, could not show convincing statistical difference between CPPS patients and normal men when measuring autoimmune reactions to prostate proteins in his 2009 study.