Influence of HLA Alleles on the Rate of Progression of Vertically Transmitted HIV Infection in Children: Association of Several HLA-DR13 Alleles with Long-Term Survivorship and the Potential Association of HLA-A2301 with Rapid Progression to AIDS

ABSTRACT Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria, a low or normal blood pressure, and hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the K and Mg levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta, coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Ca and Mg levels. Calcification is much less common in Bartter syndrome which itself is rarer and associated less often with hypomagnesemia.

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Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression

npj Genomic Medicine ◽

10.1038/s41525-021-00185-w ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Savannah Mwesigwa ◽

◽

Lesedi Williams ◽

Gaone Retshabile ◽

Eric Katagirya ◽

...

Keyword(s):

Hiv Infection ◽

Diversity Index ◽

Strong Association ◽

Community Diversity ◽

Added Value ◽

Sequencing Platform ◽

Public Health Burden ◽

Survival Status ◽

Significant Public Health

AbstractHuman immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.

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Short report: craniosynostosis, a late complication of nutritional rickets

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0580 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Lydia Y. Forestier-Zhang ◽

Paul Arundel ◽

Robyn Gilbey-Cross ◽

Mohammed Zulf Mughal ◽

Amaka C. Offiah ◽

...

Keyword(s):

Early Identification ◽

Late Complication ◽

Psychosocial Problems ◽

Short Report ◽

Delayed Presentation ◽

Brain Growth ◽

Case Presentation ◽

Nutritional Rickets ◽

Potential Association

Abstract Objectives Nutritional rickets may be a preventable cause of craniosynostosis. This potential association is under-recognised. A late diagnosis of craniosynostosis may result in reduced brain growth, raised intracranial pressure and long-term psychosocial problems. Case presentation We present four cases of craniosynostosis associated with nutritional rickets. Those who had delayed presentation underwent emergency craniotomy. Conclusions Treatment of nutritional rickets and early identification of craniosynostosis can reduce morbidity in these children.

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Combined Genotypes of CCR5, CCR2, SDF1, and HLA Genes Can Predict the Long-Term Nonprogressor Status in Human Immunodeficiency Virus-1–Infected Individuals

Blood ◽

10.1182/blood.v93.3.936 ◽

1999 ◽

Vol 93 (3) ◽

pp. 936-941 ◽

Cited By ~ 151

Author(s):

Magdalena Magierowska ◽

Ioannis Theodorou ◽

Patrice Debré ◽

Françoise Sanson ◽

Brigitte Autran ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Chemokine Receptor ◽

Multivariate Logistic Regression Model ◽

Hla B27 ◽

Hla Alleles ◽

Immunodeficiency Virus ◽

Combined Genotypes ◽

Hiv 1

Abstract Human immunodeficiency virus (HIV)-1–infected long-term nonprogressors (LT-NP) represent less than 5% of HIV-1–infected patients. In this work, we tried to understand whether combined genotypes of CCR5-▵32, CCR2-64I, SDF1-3′A and HLA alleles can predict the LT-NP status. Among the chemokine receptor genotypes, only the frequency of the CCR5-▵32 allele was significantly higher in LT-NP compared with the group of standard progressors. The predominant HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA-B27, HLA-DR6, and HLA-DR7. A combination of both HLA and chemokine receptor genotypes integrated in a multivariate logistic regression model showed that if a subject is heterozygous for CCR5-▵32 and homozygous for SDF1 wild type, his odds of being LT-NP are increased by 16-fold, by 47-fold when a HLA-B27 allele is present with HLA-DR6 absent, and by 47-fold also if at least three of the following alleles are present: HLA-A3, HLA-B14, HLA-B17, HLA-DR7. This model allowed a correct classification of 70% of LT-NPs and 81% of progressors, suggesting that the host’s genetic background plays an important role in the evolution of HIV-1. The chemokine receptor and chemokine genes along with the HLA genotype can serve as predictors of HIV-1 outcome for classification of HIV-1–infected subjects as LT-NPs or progressors.

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