HLA B27 information ~autoimmunity issues & how I got here~ (research compilation with reference links)

 HLA B27

In the human immune system, the HLA (human leucocyte antigen) family of genes plays an important role in defending against foreign invaders such as viruses.

The authors say that the origins of some HLA class 1 genes are proof that our ancient relatives interbred with Neanderthals and Denisovans for a period.

“Getting these genes by mating would have given an advantage to populations that acquired them.”

At least one variety of HLA gene occurs frequently in present day populations from West Asia, but is rare in Africans.


“The HLA genes that the Neanderthals and Denisovans had, had been adapted to life in Europe and Asia for several hundred thousand years, whereas the recent migrants from Africa wouldn't have had these genes,”said study leader Peter Parham from Stanford University School of Medicine in California.

“So getting these genes by mating would have given an advantage to populations that acquired them.”

Dr. Pinna says:

The HLA gene which provides our white cells in our immune system with the ability to recognize viruses and perhaps cancers was a gift from our Neanderthal ancestors.

Neanderthals interbred with Europeans and Chinese but not with Africans. This is very important from a medical point of view.

Since the HLA (HUMAN LEUKOCYTE (WHITE CELL) ANTIGEN) protects against viruses, we find the most deadly viruses in Africa. For example, the famous EBOLA virus.Why? Because Africans do not have the ability to defend against and eradicate this virus. The viruses found in Europe and China are rather mild, such as mumps, measles and German measles.Also, Africans have less defenses against cancers caused by viruses. Here is a report from the Guardian, U.K:

“The difference is that a disproportionate number of cancers in Africa are caused by infections, such as the hepatitis viruses (B and C), which cause liver cancer, or the human papillomavirus (HPV), which causes 98% of cervical cancers. The worldwide average for infection-related cancers is about 22%; in Africa, the figures are much higher: 40% of cases in women and 30% in men.”

European and Chinese interbreeding with Neanderthals was a gift from God. Not only did it give us red hair and big brains, but also a way to fight viral infection.


http://drpinna.com/neanderthal-genes-boosts-our-immune-system-23305


HLA B27 & Arthritis

Arthritis is a term for any of more than one hundred diseases that produce swelling in a joint, accompanied by pain and stiffness. The most common forms of arthritis are osteoarthritis (the degeneration of a joint) and rheumatoid arthritis ("the great crippler," inflammation of a joint that erodes bone and cartilage). Other forms include ankylosing spondylitis (inflammation of spinal joints, mainly affecting young men), infectious arthritis (caused by invading microorganisms), and chronic Lyme arthritis (which appears in some people who contract Lyme disease). Lupus, an autoimmune disease, also has elements of arthritis, with painful and often swollen joints.

Neanderthal skeletons show signs of arthritis, as do Egyptian mummies. Ancient Greek and Roman physicians wrote detailed descriptions of arthritic conditions and methods of treatment. In fourteenth- and fifteenth-century Europe, gout became common among members of the upper classes, and an outbreak of rheumatoid arthritis swept through the masses of Europe during the Industrial Revolution. By the early nineteenth century, rheumatoid arthritis had been recognized as a distinct condition, separate from gout. Augustin Landre-Beauvais gave rheumatoid arthritis its first complete clinical description in 1800; in 1859 Alfred Garrod (1819-1907) distinguished gout by the presence of uric acid.

While the disease had been known for centuries, its cause remained unknown. Some thought arthritis was the result of an infectious disease, such as gonorrhea or tuberculosis. In 1900 twophysicians, Frederick J. Poynton (1869-1943) and A. Paine, discovered a bacteria in a group of children afflicted with rheumatism. They speculated that rheumatic arthritis could be the result of an immune reaction to an invading microorganism. In 1940 researchers found an rheumatoid factor, an antibody-like substance, in the blood of arthritis patients. Further study showed that rheumatic infections were caused by a group A streptococcus, so the rheumatoid factor was indeed an immune system response to that bacteria. Current research focuses on the relationship between specific genetically coded HLA molecules (an element of the immune system) and the occurrence of various types of arthritis. For example, the HLA-B27 molecule is common in people with ankylosing spondylitis.[14]


HLA B27 & CCR5-Δ32


According to Randall Johnson at the Baylor College of Medicine in Houston, "Only 7% of the US population tests positive for the HLA-B27 gene; this gene, found only in persons with Rh-Negative blood, can trigger the immune system to operate overtime at WARP SPEED in times of medical emergency."


Note: HLA-B27 is also sometimes found in those who are Rh negative recessive.


The HLA-B27 Genetic Marker is said to have protective properties that guard against the progression of HIV. It is said, that people with this gene do not have the right proteins for the HIV virus to bind with. The HLA-B27 Marker is most often found in people with O- Blood.


CCR5-Δ32 is a deletion mutation of a gene that has a specific impact on the function of T cells. At least one copy of CCR5-Δ32 is found in about (5-14%) of people of Northern European and in those of Northern European descent. There also is a small minority (1%) with the same mutation amongst Southern Europeans or Balkan Peninsula. It has been hypothesized that this allele was favored by natural selection during the Black Death for Northern Europeans.


The allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV. Yersinia pestis (the bubonic plague bacterium) was demonstrated in the laboratory not to associate with CCR5. Individuals with the Δ32 allele of CCR5 are healthy, suggesting that CCR5 is largely dispensable. However, CCR5 apparently plays a role in mediating resistance to West Nile virus infection in humans, as CCR5-Δ32 individuals have shown to be disproportionately at higher risk of West Nile virus in studies, indicating that not all of the functions of CCR5 may be compensated by other receptors.

While CCR5 has multiple variants in its coding region, the deletion of a 32-bp segment results in a nonfunctional receptor, thus preventing HIV R5 entry; two copies of this allele provide strong protection against HIV infection. This allele is found in 5–14% of Europeans but is rare in Africans and Asians.


HLA-B27 is an inherited gene marker that is associated with a number of related rheumatic diseases. They share in common, certain features like spinal and peripheral arthritis, skin and GI disorders, anterior chamber eye disease, psoriasis like skin lesions, as well as inflammation and joint pain. This gene is found with highest prevalence in patients with ankylosing spondylosis, reactive arthritis, and patients with the combination of peripheral arthritis and either psoriasis or inflammatory bowel disease.


Neanderthals have been found with skeletal deformities known to be caused be ankylosing spondylitis and Arthritis.[13]


CONCLUSION


Neanderthals carried HLA-B27 which offers protection from certain diseases, however it also causes autoimmune diseases. CCR5-Δ32 deletion is also linked in with O negative blood. They originate in Neanderthals and are not often found in Africa. If you have Rh negative blood, you are blessed with some of the genes from our most ancient families.

Research by Tia Douglass & Andre Heyrman of NADA.

REFERENCE:
Matt McGrath
http://rhnegativebloodsecrets.blogspot.com/2013/01/are-you-related-to-neanderthals.html?m=1

If you're feeling sad ~ don't read

Thoughts from a burdened mind..

I don't dream of compassion or hunger for your attention anymore. I used to think it would make me feel better, I thought it would help the hurt.. 

But you had too much of your own, I forgive you abandoning me even when you were there. 

And those times I was beat up on the inside which made the outside seem even more bleak.. it hurts to know it was you helping torture my esteem, 

I forgive you for ever treating me mean. 

I don't cast stones or arrows, I merely wish you love! & if I could change a thing that ever harmed, please know I would! 

I've said goodbye to living in a number of ways but kept existing just the same. .So many apologies of my own to make.

 Must've done some truly wicked things to land this lot that's been handed me. So that being the case I'll bare it, true but, it doesn't mean it should also afflict you. 

Keeping inner demons at rest is a struggle, when you lay quietly waiting for sweet death they come flooding in like old familiar songs.

 I've wrestled and fought with illness, myself, and the ones I love... I don't know what I'm supposed to do now, it seems God doesn't even want me above. .

.. the future is bleak & I'm already a burden it's true, if I could sneak away to some shack, I promise that's what I'd do. 

I'm in pain everyday now but it's not because of you. I keep it to myself if I can .. trying not to let it show. I vent & purge occasionally, sorry if you overheard.

Bathroom floor

Chronically Ill.. ?!  

But..

.. you don't look sick.

..you were just out yesterday.

.. oh, you're too young to sit around, etc...

Oh, come on & join us, you'll have fun getting out.. Or

Don't invite her, she won't come anyway.

Lazy.

Excuses, excuses....

Those are just a few phrases you might hear on any given day ~ maybe even from someone you love (it might even be yourself).

 Forgive them, they know not what they do. 

Today, for instance; I woke from one of the best sleeps I've had in ages. Yes, I woke at 4am but that's OK. 

I was able to move from the bed for coffee (1/2caf) without too much ado so, I decided to do something that seriously required attention but wouldn't take any herculean effort, my hair.  It's long & unruly with that Poliosis skunk stripe that I'm confused on managing, plus it hadn't been cut in years. 

I set myself up at the bathroom vanity and began sectioning, so far, so good. I can do this!

 I even brought a bar stool to sit occasionally, no worries. 

I clipped a few inches away & allot of bulk that made my neck feel lighter. Success! 

Wow, I'm doing good, I'm gonna style it & maybe even make it one of the very rare days with cosmetics....

Well, with all my high hopes of taking a selfie & prancing my preened self in public.... I compose this message to you now from the bathroom floor. Some days even with the best intentions & efforts it just doesn't work out. Luckily, no ones invited or expecting me any where. I'll just wait the pain out here, disappointing no one but myself.

Today is still a good day! There are lots of daylight hours left and if this is the worst that happens, I'm still doing well comparatively. 

http://www.dercumsdiseasefoundation.com/home.html

About our DNA .....

PREVALENCE
The prevalence of HLA-B27 varies between populations— from 50% in Haida Indians to 0/ nil in Australian Aborigines. In the UK general population it is about 8%. HLA-B27 is rare in the American black population whereas Eskimo populations carry it much more frequently than Western Europeans, with prevalence rates of 25% or more. This antigen is associated with ankylosing spondylitis in virtually all racial groups studied. 

PATHOGENESIS
HLA-B27 positive Caucasians have a 20-fold risk of developing any spondylarthropathy, particularly ankylosing spondylitis and undifferentiated spondarthritis.

Family and twin studies of ankylosing spondylitis have shown a polygenic pattern of genetic susceptibility with heritability in excess of 90%. The contribution of HLA-B27 to genetic susceptibility has been estimated to be 20–50% of the total.

Other HLA alleles, most notably HLA-B60 and HLA-DR1, may predispose to ankylosing spondylitis either independently of B27 or in conjunction with it.

MECHANISMS
The main natural function of HLA-B27 is to form a complex with β2microglobulin which can bind short antigenic peptides such as those derived from intracellular microorganisms. Following presentation at the cell surface, the complexes are specifically recognised by cytotoxic lymphocytes which then kill the infected cell.

Viral?/Organisms have been shown to trigger reactive arthritis, including Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia, Mycobacteria and possibly Brucella, all of which habitually survive intracellularly. HLA-B27 appears to enhance the invasion of Salmonella into intestinal epithelial cells.

PREDICTIVE
{Insert genome suscept.
-first degree}
Generally, the value of testing for HLA-B27 depends upon the particular clinical situation. Beginning with a clinical estimate of the likelihood of ankylosing spondylitis or a related spondarthropathy.

Seronegative Spondarthritides

Ankylosing spondylitis
Reactive arthritis (Reiter’s syndrome)
Psoriatic arthropathy
Enteropathic arthropathy
Acute anterior uveitis
Juvenile spondarthritis
Undifferentiated spondarthritis
Isolated peripheral enthesitis

ASSOCIATIONS
HLA-B27 and ankylosing spondylitis remains the strongest known relationship between a major histocompatibility complex (MHC) antigen and a disease!

Enthesitis, defined as inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis and joint capsules, is a hallmark.

The concept of entheseal organ prone to pathological changes in spondyloarthritis is well recognized.

The relevant role of peripheral enthesitis is supported (heel pain or other well-defined enthesopathic pain), axial and peripheral spondyloarthritis.

Episodes of Achilles tendinitis, plantar fasciitis, posterior tibial tendinitis, & dactylitis. Also seen are lateral epicondyle, insertion of the patella tendon into the inferior pole of the patella, femoral quadriceps, and posterior tibial tendons. {continue}Hip disfunct:

Upper lobe fibrosis is the lung condition best known to correlate with HLA-B27.  The antigen may be positively, neutrally or negatively associated with asbestosis. Claims have also been made for an association with other pulmonary diseases, especially pleurisy, pleural abscess, bronchitis and pneumonia and pneumothorax, independently of the presence of ankylosing spondylitis.

Aortic regurgitation occurs in 2–10% of patients with ankylosing spondylitis, and cardiac conduction abnormalities including atrioventricular and intraventricular blocks have been found in one-third of patients with spondylitis.

HLA-B27 related cardiac lesions may be found in the absence of other rheumatological manifestations.
Indeed, an HLA-B27 associated cardiac syndrome comprising severe cardiac conduction system abnormalities and lone aortic regurgitation has been defined, whose link with B27 is almost as strong as that between B27 and ankylosing spondylitis.

Significant association has been reported between HLA-B27 and acute leukaemia, particularly acute myeloid leukaemia.HLA-B27 carriers may have an increased risk of acute leukaemia whilst those with concomitant ankylosing spondylitis may be predisposed to lymphoid malignancies.

While infection with HIV predisposes to spondyloarthropathy,HLA-B27 is the HLA class I molecule most closely associated with non-progression of HIV infection to AIDS.

HLA-B27 can be helpful in a patient complaining of low back pain of an inflammatory character in the absence of radiological signs of sacroiliitis or in patients with an asymmetrical oligoarthritis but without other features of spondarthritis. This has been acknowledged with the inclusion of HLA-B27 positivity as a criterion in the Amor classification criteria for spondyloarthropathy.

Likewise, testing for HLA-B27 can help to differentiate between alternative aetiologies in iritis and aortic regurgitation.

PROGNOSTIC VALUE

Whereas HLA-B27 does not seem to influence the severity of ankylosing spondylitis, in psoriatic spondylarthropathy it may determine not only susceptibility to the condition but also its clinical expression.

It correlates most strongly with isolated axial disease and it may confer some protection against peripheral joint erosions.

Patients with Reiter’s disease and Yersinia andSalmonella triggered reactive arthritis who are HLA-B27 positive have more severe acute disease, more extra-articular features and more frequent chronic back pain and sacro-iliitis.

In C. trachomatis reactive arthritis, more severe or chronic disease could be due to lower concentrations of interferon-γ in the synovial fluid of patients who are HLA-B27 positive than those who are HLA-B27 negative, with consequent impaired clearance of infective agents.

With regard to cardiac disease, the relative risk that a HLA-B27 positive man will need a permanent pacemaker has been calculated to be 6.7 compared with a man who has other B alleles. This association is not, however, present in female patients.

A poor outcome of back surgery has been found in patients possessing HLA-B27.

Atlanto-axial subluxation can occur.

HLA-B27 positive patients with rheumatoid arthritis have about twice the risk of developing subluxation of the cervical spine and an almost threefold risk of subaxial subluxation.

Thus, HLA-B27 may transpire to be a useful prognostic indicator for the later development of instability of the cervical spine and its complications in rheumatoid arthritis.

The discovery of the link between HLA-B27 and a large family of inflammatory rheumatic diseases was one of the seminal advances in rheumatology in the last century. Associations have subsequently been identified with other musculoskeletal and non-rheumatic diseases.

The Test
http://labtestsonline.org/understanding/analytes/hla-b27/tab/test/

The HLA-B27 test is primarily ordered to help strengthen or confirm a suspected diagnosis of ankylosing spondylitis (AS),reactive arthritis, juvenile rheumatoid arthritis (JRA), or sometimes anterioruveitis. The HLA-B27 test is not a definitive test that can be used to diagnose or rule out a disorder. It is one piece of evidence used along with the evaluation of signs,symptoms, and other laboratory tests to support or rule out the diagnosis of certain autoimmune disorders, such as ankylosing spondylitis and reactive arthritis.

Ankylosing spondylitis and reactive arthritis are both chronic, progressive conditions that occur more frequently in men than women. The first symptoms typically occur when a person is in their early 30's. Often, the initial symptoms of these autoimmune disorders are subtle and may take several years before characteristic degenerative changes to bones and joints are visible on X-rays.

Ankylosing spondylitis is characterized by pain, inflammation, and a gradual stiffening of the spine, neck and chest.Reactive arthritis is a group of symptoms that includes inflammation of the joints,urethra, and eyes as well as skin lesions.Juvenile rheumatoid arthritis is a form ofarthritis that occurs in children.Anterior uveitis is associated with recurring inflammation of the structures of one or both eyes.

The HLA-B27 test may be ordered as part of a group of tests used to diagnose and evaluate conditions causing arthritis-like chronic joint pain, stiffness, and inflammation. This group of tests may include an RF (rheumatoid factor) with either an ESR (erythrocyte sedimentation rate) or a CRP (C-reactive protein). HLA-B27 is sometimes ordered to help evaluate someone with recurrent uveitis that is not caused by a recognizable disease process.

When is it ordered?

An HLA-B27 test may be ordered when a person has acute or chronic pain andinflammation in the spine, neck, chest, eyes, and/or joints, and the doctor suspects the cause is an autoimmune disorder that is associated with the presence of HLA-B27. An HLA-B27 may also be ordered when someone has recurrent uveitis.

The HLA-B27 test is not diagnostic, but the results add information, increasing or decreasing the likelihood that the person being evaluated has the suspected autoimmune disorder.

Doctors frequently use the HLA-B27 test result when they suspect ankylosing spondylitis but the disease is in an early stage and the vertebrae in the spine have not yet undergone the characteristic changes that would be seen on X-ray.

What does the test result mean?

If a person is positive for HLA-B27 and has symptoms such as chronic pain,inflammation, and/ or degenerative changes to his bones (as seen on X-ray), then it supports a diagnosis of ankylosing spondylitis, reactive arthritis, or anotherautoimmune disorder that is associated with the presence of HLA-B27. This is especially true if the person is young, male, and if he experienced his first symptoms before the age of 40.

If HLA-B27 is negative, then the marker was not detected. This does not mean, however, that the person tested does not have the suspected condition since people who do not have the HLA-B27 antigen can also develop these autoimmune diseases. Likewise, someone who has the HLA-B27 antigen will not necessarily develop one of these conditions. Researchers are trying to determine what factors contribute to the higher likelihood of people with HLA-B27 developing these particular diseases and what actually triggers them.

Whether or not certain HLA antigens will be present is genetically determined. Their production is controlled by genes that are passed from parents to their children. If two members of the same family are HLA-B27 positive and one of them develops a disease associated with HLA-B27, then the other person is at an increased risk of developing a similar disease.

Is there anything else I should know?

Though the diseases associated with HLA-B27 occur more frequently in men, women can also be affected. However, the signs and symptoms related to the diseases can often be milder in women.

With new genetic testing methods, it is now possible to separate HLA-B27 into subtypes. So far, more than 70 different subtypes have been identified, such as HLA B27*05 and HLA B27*02. How the presence of these specific subtypes affects the likelihood of developing an autoimmune disease is not yet known

Important to speak to first degree relatives... !

It is important to inform first degree relatives regarding genetic predilection to associated conditions & syndromes in light of a positive HLA B27 result..

http://ghr.nlm.nih.gov/glossary=firstdegreerelative