Functional complement analysis can predict genetic testing results and long-term outcome in patients with complement deficiencies

Background: Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries. Objective: The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD. Methods: CD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD. Results: Genetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5–6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported. Conclusion: Results of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD

Stevens-Johnsonov sindrom in toksična epidermalna nekroliza pri otrocih: prikaz primerov in pregled literature

Stevens-Johnsonov sindrom (SJS) in toksična epidermalna nekroliza (TEN) sta redki življenje ogrožajoči bolezni, ki se kažeta z nastajanjem mehurjev ter odstopanjem povrhnjice kože in sluznic. Najpogosteje sta posledica imunsko sprožene reakcije na zdravilo, redkeje zaradi drugih vzrokov. Poleg prekinitve zdravljenja z zdravilom, ki je lahko sprožilo SJS/TEN, ali uvedbe zdravljenja bakterijske okužbe, če je ta kot vzročni dejavnik dokazana, uvedemo lokalno zdravljenje sprememb na očeh, koži in sluznicah, v težjih primerih pa še sistemsko zdravljenje z glukokortikosteroidi (GKS) in/ali intravenskimi imunoglobulini (IVIG). Za optimalni izid bolezni je bistveno sodelovanje med specialisti različnih strok. Prispevek predstavi skupino bolnikov, obravnavanih na Kliničnem oddelku za otroško alergologijo, revmatologijo in klinično imunologijo Pediatrične klinike UKC v Ljubljani in pregled literature. V letih 2011–2019 smo zdravili šest otrok s SJS/TEN. Pri štirih otrocih je bil sprožilni dejavnik zdravilo, pri enem okužba z Mycoplasmo pneumonie, pri enem bolniku pa etiologije nismo mogli opredeliti. Z GKS in IVIG so bili zdravljeni štirje otroci, en otrok z okužbo z M. pneumonie je bil zdravljen z azitromicinom in IVIG, en otrok pa je prejel le zdravila lokalno. Izid bolezni je bil pri vseh otrocih dober, in sicer tudi brez poznih posledic bolezni

Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies

BackgroundPrevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries.ObjectiveThe purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD.MethodsCD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD.ResultsGenetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5–6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported.ConclusionResults of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD

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Background<p>Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries.</p>Objective<p>The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD.</p>Methods<p>CD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD.</p>Results<p>Genetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5–6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported.</p>Conclusion<p>Results of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD.</p