Severe cutaneous human papillomavirus infection associated with natural killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

Kamili, Qurat Ul Ain; Seeborg, Filiz O.; Saxena, Kapil; Nicholas, Sarah K.; Banerjee, Pinaki P.; Angelo, Laura S.; Mace, Emily M.; Forbes, Lisa R.; Martinez, Caridad; Wright, Teresa S.; Hanson, I. Celine

doi:10.1016/j.jaci.2014.07.009

Cited by 27 publications

(17 citation statements)

References 8 publications

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“…We also report the first substantial gene marking and correction of NK cells in SCID-X1 after gene therapy with substantial clinical improvement of warts and molluscum (31). In contrast to the rapid expansion of gene-corrected T cells in SCID-X1 infants after gene therapy, the T cell marking in adult P1 and P2 increased slowly.…”

Section: Discussionmentioning

confidence: 90%

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

et al. 2016

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X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.

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Section: Discussionmentioning

confidence: 90%

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

et al. 2016

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“…Further work is required to show the importance of our findings for the susceptibility to HPV infection in a γc-deficient context in vivo and to investigate the contribution of other cell types that also express receptors for CXCL1 and CXCL8 (Inngjerdingen et al, 2001). In particular, analyzing the role of natural killer cells would be of interest because poor natural killer cell engraftment was associated with HPV infection in a small cohort of X-SCID patients (Kamili et al, 2014). …”

Section: Resultsmentioning

confidence: 99%

“…However, despite excellent long-term survival after curative therapy, a persistent susceptibility to human papillomavirus (HPV) infections is well described that does not appear overall to relate to the conditions of transplantation or immune reconstitution (Gaspar et al, 2004a; Laffort et al, 2004). In several independent studies, up to 64% of treated children developed warts, with lesion onset 4 to 19 years after transplantation (Abd Hamid et al, 2017; Gaspar et al, 2004a; Kamili et al, 2014; Laffort et al, 2004). …”

Section: Introductionmentioning

confidence: 99%

Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment

Nowak

Linzner

Thrasher

et al. 2017

Journal of Investigative Dermatology

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Loss-of-function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency characterized by lack of T and natural killer cells and infant death from infection. Hematopoietic stem cell transplantation or gene therapy offer a cure, but despite successful replacement of lymphoid immune lineages, a long-term risk of severe cutaneous human papilloma virus infections persists, possibly related to persistent γc-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional γc and its co-receptors. After stimulation with the γc-ligand IL-15, γc-deficient keratinocytes show significantly impaired secretion of specific chemokines including CXCL1, CXCL8, and CCL20, resulting in reduced chemotaxis of dendritic cells and CD4+ T cells. Furthermore, γc-deficient keratinocytes also exhibit defective induction of T-cell chemotaxis in a model of stable human papilloma virus-18 infection. These findings suggest that persistent γc-deficiency in keratinocytes alters immune cell recruitment to the skin, which may contribute to the development and persistence of warts in this condition and would require different treatment approaches.

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“…However, there are times when the immune system is not able to control the progression of HPV infections or is unable to prevent recurrences in patients who have already been treated. Importantly, NK deficiency has been related to an increased susceptibility to HPV infections and to a loss of control of them, as well as to a greater appearance of cervical cancer [39][40][41][42]. Considering this, it is logical to think that helping the systemic cell-mediated immune system to fight HPV should improve the prognosis of infections by this virus.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Oral Supplementation with a Casein Hydrolysate-based Formula to Favor the Clearance of HR-HPV Infections and their Derived Lesions

Pingarrón¹,

Duque²,

López³

et al. 2019

Preprint

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Cervical cancer screening systems aim to detect established HPV infections early. However, if there are no high-grade lesions, the intervention choice is basically limited to observational follow-up with recommendations on life habits like diet, to favor infection control. Therefore, it is important to establish specific feeding guidelines that provide clear evidence about the benefit they may bring against HPV infections. The present study evaluates the benefits of nutritional supplementation with a casein hydrolysate-based formula in patients with HR-HPV infection, compared with a non-supplemented control group. A total of 118 patients completed 6 months of follow-up. Significant differences between supplemented and control groups were observed for total or partial HR-HPV clearance at 6 months (74.6% vs 35.6%). Supplemented patients also suffered a lower occurrence of new intracervical lesions (0% vs 28.6%), a significantly greater resolution (67.4% vs 41.9%) and less progression of pre-existing lesions (4.7% vs 9.7%) at 6 months. An increase in the effectors of cellular immunity that could be responsible for their effect was also observed in supplemented patients. We conclude that nutritional supplementation with this casein hydrolysate-based formula could improve the outcomes of observational management of HPV infection.

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Severe cutaneous human papillomavirus infection associated with natural killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

Abstract: Capsule Summary The authors identify Natural Killer cell deficiency in post-transplant severe combined immunodeficiency patients who developed severe human papilloma virus infections as a long term complication.

Cited by 27 publications

References 8 publications

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment

Evaluation of Oral Supplementation with a Casein Hydrolysate-based Formula to Favor the Clearance of HR-HPV Infections and their Derived Lesions

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