Normal hydroxylation of proline in collagen synthesized by skin fibroblasts from a patient with prolidase deficiency

Royce, Peter M.; Danks, David M.

doi:10.1007/bf01800003

Cited by 7 publications

(3 citation statements)

References 19 publications

(34 reference statements)

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“…Pt1 presented with a more aggressive inflammatory disease with severe skin manifestations and autoimmunity, while Pt2 presented with more atopy. Different PD phenotypes between siblings have been previously reported and varying environmental factors or epigenetic modulators have been proposed as causative [ 5 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

Alrumayyan

Slauenwhite

McAlpine

et al. 2022

Allergy Asthma Clin Immunol

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Background Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used. Case presentation Patient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high. Conclusions Immunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

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Section: Discussionmentioning

confidence: 99%

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

Alrumayyan

Slauenwhite

McAlpine

et al. 2022

Allergy Asthma Clin Immunol

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“…at 4°C, and treated with bacterial collagenase either directly or after prior pepsin digestion, both as described above. The extent of prolyl hydroxylation in such proteins was determined by measuring the distribution of radioactivity between proline and hydroxyproline in acid hydrolysates of collagenase-digestible material as described previously [32], except that the column eluant was 0.2 M sodium citrate, pH 3.1.…”

Section: Determination Of Extent Of Prolyl Hydroxylationmentioning

confidence: 99%

Biosynthesis of recombinant human pro-α1(III) chains in a baculovirus expression system: production of disulphide-bonded and non-disulphide-bonded species containing full-length triple helices

Tomita

Ohkura

Ito

et al. 1995

Biochemical Journal

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We have investigated the expression of human procollagen III by insect cells infected with a recombinant baculovirus carrying cDNA for the pro-alpha1(III) chain of type-III collagen. A high level of expression was obtained, and a small proportion of the heterologously expressed pro-alpha1(III) chains formed normally disulphide-bonded procollagen III, which was secreted into the culture medium. This species displayed a melting temperature (Tm) of approx. 38 degrees C as assessed by its resistance to digestion by a mixture of trypsin and chymotrypsin, slightly lower than that of 39.5 degrees C for procollagen III synthesized by cultured human dermal fibroblasts, and reflected a slight degree of under-hydroxylation of prolyl residues. This is possibly a consequence of the lower incubation temperature of insect cells, or of an insufficiency of prolyl hydroxylase activity within them. A significant proportion of the expressed chains formed trimeric molecules of similar thermal stability containing an apparently full-length triple-helical region, but were not disulphide-bonded and not secreted. In addition to providing a source of recombinant human procollagen III, the system promises to be useful in the study of procollagen chain association and subsequent folding.

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“…Prolidase deficiency is an inborn error of metabolism mainly associated with recurrent skin ulcers [Goodman et al, 1968;Buist et al, 1972;Lapiere and Nusgens, 1969;Nusgens and Lapiere, 1973;Johnstone et al, 1974;Powell et al, 1974Powell et al, , 1977Jackson et al, 1975;Powell and Maniscalco, 1976;Faull et al, 1976;Sheffield et al, 1977;Royce and Danks, 1982;Kodama et al, 1976;Umemura, 1978;Arata et al, 1979;Isemura et al, 1979;Gejyo et al, 1980;Isemura et al, 1981;Ogata et al, 1981;Endo and Matsuda, 1981;Endo et al, 1982;Charpentier et al, 1981;Myara et al, 1983;Pedersen et al, 1983;Gray et al, 19831. Additional associated findings include other dermatological manifestations, mental retardation, splenomegaly and developmental abnormalities.…”

Section: Introductionmentioning

confidence: 97%

Clinical and biochemical characteristics of prolidase deficiency in siblings

et al. 1984

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Two brothers with recurrent skin ulcers of the lower limbs, subnormal intelligence, developmental abnormalities, and poliosis were found to excrete large quantities of several imidodipeptides in their urine. Glycylproline was the most prominent imidodipeptide excreted and was also detected in their blood. Prolidase activity was markedly deficient in red blood cells from both patients (4.1% and 3.7% of control mean) and skin fibroblasts from the one brother so examined (3.7% of control mean). A total of 20 patients with prolidase deficiency, including the two in this report, have been described in the literature. Their manifestations and various attempts at treatment are reviewed.

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Normal hydroxylation of proline in collagen synthesized by skin fibroblasts from a patient with prolidase deficiency

Cited by 7 publications

References 19 publications

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

Biosynthesis of recombinant human pro-α1(III) chains in a baculovirus expression system: production of disulphide-bonded and non-disulphide-bonded species containing full-length triple helices

Clinical and biochemical characteristics of prolidase deficiency in siblings

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