Is There a Link Between HLA–Cw6 and Psoriasis?

The exact cause of psoriasis is hard to ascertain owing to the nature of this disease. Psoriasis is a skin condition believed to have a genetic link and associated with HLA-CW6. Let us understand the relationship between HLA-CW6 and psoriasis in detail.

The frequency of presence of this allele i.e. HLA-Cw6 is found to be more prominent in Caucasian people than in Asians. This association is shown to prove a 10-fold increased risk among white people who carry this allele.1

This article delves into the literature concerned about various aspects of psoriasis, which includes pathogenesis, phenotypic characteristics, an association of the disease with various factors like alleles as well as other factors, epidemiology, and treatment aspects of psoriasis-related to HLA-Cw6.

Is There a Link Between HLA–Cw6 and Psoriasis?

Psoriasis depends upon a myriad of factors and is in direct relation to the genes. On such allele is HLA-Cw6 which makes the patient highly susceptible to psoriasis. HLA- Cw6 is observed to cause a change in the phenotypic features, comorbidities and treatment outcomes. The role of this allele is still quite unclear as far as psoriasis is concerned. HLA- Cw6 is usually concerned with type I psoriasis i.e. early-onset psoriasis.2 The symptoms of this type of psoriasis include stress, obesity, and streptococcal pharyngitis. In addition to these symptoms, certain patients have known to experience problems with arm, leg, and trunk and some show Koebner phenomenon. Patients with psoriasis and HLA-Cw6 are known to show cutaneous symptoms before the onset of musculoskeletal symptoms. This allele is responsive to methotrexate and ustekinumab.

Studies suggest that the frequency of the HLA-Cw6 allele varies drastically from 14.1 percent to 59.1 percent whereas the patients with psoriasis carrying HLA-Cw6 ranges from 10.5 percent to 77.2 percent.3 Such diversity is attributed to small sample space, ethnicity and inclusion criteria.

This also shows a difference in HLA-Cw6 distribution. HLA-Cw6 positivity is seen to be higher among the Caucasian population than Asians.3

Research has shown that there is a higher risk of psoriasis in the East of Africa than in the West of Africa. This difference in the frequency is attributed to the difference in environmental conditions like humidity and certain gene pool. Tiilikainen et. al (1980) observed that HLA-Cw6 was present in 72.7 percent patients with psoriasis-guttate in his study and 45.9 percent in patients with psoriasis-vulgaris.1

Some studies have also shown that there is no correlation between HLA-Cw6 and the ancestors of an individual. Sometimes, there is a presence of recessive inheritance or other alleles that can affect the heritability of psoriasis. The presence of the HLA-Cw6 allele does not ensure that psoriasis will be present as it also depends on various other factors as well like environment, immunology, and genetics, etc.

Involvement of HLA-Cw6 in Psoriasis Pathogenesis: Although research has shown a strong linkage between HLA-Cw6 and psoriasis, the function of this allele is not reviewed as much. It has been observed that HLA-Cw6 can affect both adaptive as well as the innate immune system. It affects the innate immune system by combining with the killer immunoglobulin receptors, which have been associated with psoriasis in the past.

HLA-CW6 and Psoriasis -Disease Aggravating Factors

When considering HLA-CW6 and psoriasis, we must consider the various disease aggravating factors.

  • Age of Onset: HLA-Cw6 allele is strongly associated with greater severity of symptoms of psoriasis. Thus, HLA-Cw6 status can be a strong indicator of psoriasis onset and severity.
  • Pregnancy: Women who showed positive HLA-Cw6 experienced more remissions during the period of pregnancy. This remission is common during pregnancy for patients with autoimmune diseases like rheumatoid arthritis.
  • Lifestyle: Psoriasis-like any other disease is affected by the lifestyle choices of a person. Factors like smoking and stress can increase the risk of early-onset and deterioration of existing psoriasis.
  • Weight: Weight and greater body mass index is a strong factor determining the risk of psoriasis. While HLA-Cw6 and psoriasis have a link, greater body weight can add to the risk.

Treatment of Psoriasis

Psoriasis is one of the multifactorial diseases that has a strong genetic background and HLA-Cw6 is one of its alleles having a strong psoriasis susceptibility. It is observed that HLA-Cw6 affects the course of the disease, features of phenotypic, severity, comorbidities as well as the outcomes of its treatment. Since the early 19th century, Psoriasis is being studied as a separate skin disease but the exact trigger has still not been found. Though the major risk allele for psoriasis is the allele HLA-Cw6, its penetrance was observed to be very less. As there are many other factors too playing an important role, the diagnosis and treatment of psoriasis very crucial.

The diagnosis of psoriasis is done through two ways, i.e., with the help of a physical examination and with the medical history of the patient. The other way to find out is a skin biopsy, which is examined under a small microscope to rule out other disorders.

Systemic Treatment For Psoriasis

Although HLA-Cw6 and psoriasis are found to be linked, appropriate treatment should be given. A systematic procedure is required to treat psoriasis. Various pharmacogenomic and pharmacogenetic studies have been conducted on this topic, which showed that the most common treatments provided for a patient with psoriasis include ciclosporin, fumaric acid esters, methotrexate, phototherapy, and retinoids. HLA-Cw6 gene is linked to responsiveness with methotrexate. HLA-Cw6 positive patients are more responsive to the conventional treatment involving anti-psoriasis because the HLA-Cw6 positive rate is seen to be less in patients who have severe psoriasis and have already failed to respond to anti-psoriasis therapies.

With the help of the treatment, the inflammation is reduced and skin is cleared. The treatment for psoriasis includes:

Topical Treatments – Mild or moderate Psoriasis can be healed with the help of the application of oil or cream. If the disease is severe, creams should be combined with light therapy or oral medications. This treatment includes –

Topical Corticosteroids – This drug is prescribed for the treatment of mild to moderate Psoriasis as it helps in the reduction of inflammation and stops the itching. It can also be used along with any other treatment that is going on. Mild Corticosteroid ointment is generally recommended for areas that are sensitive like the face or skin folds. It is also applied for the treatment of wide patches of damaged skin. But using it for a long time can cause thinning of the skin and it may even stop working when used continuously.

Vitamin D Analogues – The synthetic form of this vitamin helps in slow skin cell growth. Dovonex is one such solution that contains vitamin D and heals mild to moderate Psoriasis.

Anthralin – It helps in slow skin cell growth while removing the scales and making the skin smoother with time.

Topical Retinoids – It helps in decreasing the skin inflammation as it has vitamin A in it but the most common side effect for the same is skin irritation. It also causes an increase in sunlight sensitivity. So, it is advised to apply sunscreen before stepping out in daylight.

Coal Tar – It is derived from coal, as the name suggests. It is essential in reducing inflammation, itchiness, and scaling. But the issue with coal tar is that it can cause skin irritation, is messy and can cause a stain on the clothes. It also has a strong odor. This treatment is not recommended for pregnant or breastfeeding women.

Conclusion

Psoriasis is affected on various fronts due to the presence of an allele, hence HLA-Cw6 and psoriasis are thought to be related. These aspects include genetic factors, comorbidity, treatment aspect as well as clinical manifestation. There has been recent research in this field which shows that the two autoantigens namely LL-37 and ADAMTSL5 show a high affinity to bind with HLA-Cw6. There has been a positive response to the treatment both in the form of conventional agents as well as biological treatment.

However, the myriad number of psoriasis pathogenesis and the association of HLA-Cw6 and psoriasis needs more research.

References:

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