Cargando…
Clinical features of patients with homozygous complement C4A or C4B deficiency
INTRODUCTION: Homozygous deficiencies of complement C4A or C4B are detected in 1–10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013154/ https://www.ncbi.nlm.nih.gov/pubmed/29928053 http://dx.doi.org/10.1371/journal.pone.0199305 |
_version_ | 1783333972836614144 |
---|---|
author | Liesmaa, Inka Paakkanen, Riitta Järvinen, Asko Valtonen, Ville Lokki, Marja-Liisa |
author_facet | Liesmaa, Inka Paakkanen, Riitta Järvinen, Asko Valtonen, Ville Lokki, Marja-Liisa |
author_sort | Liesmaa, Inka |
collection | PubMed |
description | INTRODUCTION: Homozygous deficiencies of complement C4A or C4B are detected in 1–10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. MATERIAL AND METHODS: Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients’ files. RESULTS: Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83–158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00–1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79–2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30–7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22–4.88, p = 0.010). CONCLUSION: This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations. |
format | Online Article Text |
id | pubmed-6013154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60131542018-07-06 Clinical features of patients with homozygous complement C4A or C4B deficiency Liesmaa, Inka Paakkanen, Riitta Järvinen, Asko Valtonen, Ville Lokki, Marja-Liisa PLoS One Research Article INTRODUCTION: Homozygous deficiencies of complement C4A or C4B are detected in 1–10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. MATERIAL AND METHODS: Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients’ files. RESULTS: Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83–158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00–1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79–2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30–7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22–4.88, p = 0.010). CONCLUSION: This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations. Public Library of Science 2018-06-21 /pmc/articles/PMC6013154/ /pubmed/29928053 http://dx.doi.org/10.1371/journal.pone.0199305 Text en © 2018 Liesmaa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Liesmaa, Inka Paakkanen, Riitta Järvinen, Asko Valtonen, Ville Lokki, Marja-Liisa Clinical features of patients with homozygous complement C4A or C4B deficiency |
title | Clinical features of patients with homozygous complement C4A or C4B deficiency |
title_full | Clinical features of patients with homozygous complement C4A or C4B deficiency |
title_fullStr | Clinical features of patients with homozygous complement C4A or C4B deficiency |
title_full_unstemmed | Clinical features of patients with homozygous complement C4A or C4B deficiency |
title_short | Clinical features of patients with homozygous complement C4A or C4B deficiency |
title_sort | clinical features of patients with homozygous complement c4a or c4b deficiency |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013154/ https://www.ncbi.nlm.nih.gov/pubmed/29928053 http://dx.doi.org/10.1371/journal.pone.0199305 |
work_keys_str_mv | AT liesmaainka clinicalfeaturesofpatientswithhomozygouscomplementc4aorc4bdeficiency AT paakkanenriitta clinicalfeaturesofpatientswithhomozygouscomplementc4aorc4bdeficiency AT jarvinenasko clinicalfeaturesofpatientswithhomozygouscomplementc4aorc4bdeficiency AT valtonenville clinicalfeaturesofpatientswithhomozygouscomplementc4aorc4bdeficiency AT lokkimarjaliisa clinicalfeaturesofpatientswithhomozygouscomplementc4aorc4bdeficiency |