Immunoglobulins and complement factor C4 in adult rhinosinusitis

Abstract

SummaryWe assessed whether complement and its factor C4 or abnormal immunoglobulin levels are associated with chronic or recurrent rhinosinusitis. We used multiple patient and control groups to obtain clinically meaningful data. Adult chronic or recurrent rhinosinusitis and acute purulent rhinosinusitis patients were compared with unselected adults and controls without previous rhinosinusitis. Associated clinical factors were reviewed. Levels of immunoglobulins, plasma C3, C4 and classical pathway haemolytic activity were analysed. C4 immunophenotyping was used to detect C4A and C4B deficiencies as null alleles. Complement was up-regulated in rhinosinusitis. C4A nulls and low IgA, IgG, IgG1, IgG2, IgG3 and IgG4 levels were all more common in chronic or recurrent rhinosinusitis patients than in unselected and healthy controls. We searched for relevant differences between the patient groups. According to stepwise logistic regression analysis, nasal polyposis [odds ratio (OR) 10·64, 95% confidence interval (CI) 2·5-45·7, P = = == 0·001], bronchial asthma (OR 8.87, 95% CI 2·3-34·9, P = = = = 0·002), C4A null alleles (OR 5·84, 95% CI 1·4-24·9, P = = = = 0·017) and low levels of IgG4 together with either IgG1 or IgG2 (OR 15·25, 95% CI 1·4-166·8, P = = = = 0·026) were more common in chronic or recurrent rhinosinusitis than in acute rhinosinusitis patients. Isolated low IgG subclasses had limited value in patient assessment. C4A null alleles are associated with chronic or recurrent rhinosinusitis, potentially through their effect on immune defence and inflammation control. Multiple clinical and immunological parameters may need to be evaluated when searching for prognostic variables.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…[585][586][587][588][589] An association between hypoimmunoglobulinemia and CRS has been described in the literature and multiple studies have demonstrated PID as a risk factor for the development of CRS. 15,155,[590][591][592][593][594][595][596] The association is further strengthened by other studies that show an increased incidence of RS in patients with immune dysfunction. 586,587 CVID, X-linked hypogammaglobulinemia, and several other disorders of humoral immunity are frequently referenced as contributing factors to chronic or recurrent recalcitrant RS.…”

“…Two case-control studies have also examined this subject. Seppanen et al 591 compared CRS (including two thirds with CRSwNP) or RARS to ARS and controls. They demonstrated that low complement C4 levels were more associated with CRS or RARS than ARS and concluded that the isolated low IgG subclass alone had limited value in patient assessment.…”

“…Testing for PID may include quantitative serum immunoglobulins, and specific antibody responses. 155,277,585,[590][591][592]813 Certain selective Ig deficiencies may be associated with other diagnoses, such as the linkage between IgG3 deficiency and atopy, stressing the importance of an adequate assessment and treatment for allergies in these patients. 595 A systematic review of the literature for immunodeficiency treatment in CRS identified 1 randomized, double-blind cross-over trial, 2 level 2b and 3b studies each, 1 level 4 study and 6 level 5 studies as follows: Tas et al 814 performed a randomized control study using thymic hormone preparation thymostimulin (TP-1) and placebo in a crossover trial.…”

“…They demonstrated that low complement C4 levels were more associated with CRS or RARS than ARS and concluded that the isolated low IgG subclass alone had limited value in patient assessment. 591 Cui et al 484 performed a case-control study in Chinese adult patients. They found that increased levels of C3 and mannosebinding lectin (MBL, a pattern-recognition molecule that can activate the lectin pathway of complement system) might play a modulatory role in CRS development.…”

Clinical characteristics of IgA nephropathy associated with low complement 4 levels

“…47 In addition, C4 plays a defensive role against virus and encapsulated bacteria. 48,49 C4 deficiency may increase the infection chances such as acute otitis media, sinusitis, or pneumonia [49][50][51] which are the exacerbating factors for IgAN resulting in a poor prognosis. [52][53][54] Someone may presume that the low C4 levels here could be caused by the activation of complement cascade.…”