Inhibitory KIR2DL2 receptor and HHV-8 in classic or endemic Kaposi sarcoma

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Inhibitory Killer cell Immunoglobulin-like Receptors (KIR), such as KIR2DL2, can impair Natural Killer (NK) cell responses against virus-infected cells.
• KIR2DL2 has been implicated in predisposing individuals to herpesvirus-associated diseases.
• Kaposi sarcoma (KS) is a herpesvirus-associated malignancy, with classical (c-KS) and endemic (e-KS) forms.

Purpose of the Study:

• To investigate the prevalence of KIR2DL2 and Human Herpes Virus 8 (HHV8) in patients with classical and endemic Kaposi sarcoma (KS).
• To compare these prevalences with those in healthy and psoriatic patient cohorts.
• To determine the potential role of KIR2DL2 as a cofactor in KS pathogenesis.

Main Methods:

• Observational study design.
• Genotyping by PCR for KIR2DL2 and KIR2DL3 alleles in blood samples.
• HHV-8 presence analysis in blood samples from c-KS, e-KS, healthy, and psoriatic patient groups.

Main Results:

• All classical KS (c-KS) and endemic KS (e-KS) patients were HHV-8 positive. HHV-8 was detected in 26.9% of psoriatic and 19.3% of healthy subjects.
• KIR2DL2 prevalence was significantly higher in c-KS patients (76.5%) compared to e-KS patients (41.7%), psoriatic patients (34.6%), and healthy controls (43.4%) (p < 0.0001).
• Age-matched comparisons confirmed a higher prevalence of KIR2DL2 in c-KS patients.

Conclusions:

• The inhibitory KIR2DL2 genotype is a potential cofactor increasing the risk for developing classical Kaposi sarcoma (c-KS) in HHV8-positive, immunocompetent individuals.
• KIR2DL2 appears to play a less significant role in the pathogenesis of endemic Kaposi sarcoma (e-KS).
• These findings highlight the importance of genetic factors in KS development, particularly for the classical form.