Article Text

PDF

Mechanisms of fibrosis in respiratory disease
S143 Serum mannose binding lectin deficiency is present in patients with early onset interstitial pulmonary fibrosis and those with affected relatives suggesting a genetic risk factor for defects in the innate immune system
  1. V A Varney1,
  2. J Evans1,
  3. H Parnell1,
  4. A Nicholas2,
  5. B Barjardeen2,
  6. N Sumar2
  1. 1Respiratory Department, St Helier Hospital, Carshalton, Surrey, UK
  2. 2Immunology Department St Helier Hospital, Carshalton Surrey, UK

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a serious progressive lung disease with likely environmental and genetic risk factors that are thought to contribute to the disease even though their exact nature is unknown. It is increasingly recognised that siblings and close blood relatives can develop the same condition suggesting an unknown genetic predisposition.

Method We have examined the serum mannose binding lectin levels (MBL) in healthy controls (HC), frequently exacerbating COPD, pulmonary TB & Sarcoidosis along with IPF patients.

Results Mean serum MBL levels were not statistically different in HC, COPD or TB using an unpaired t test. Cases with sarcoid had higher levels. Those with IPF onset at <50 years old and those with affected blood relatives (FH) had significantly reduced levels compared with IPF onset >50 years without a family history. Abstract S143 Table 1 shows means, SEM and p values, and the per cent of each patient group with normal >650, moderate 100–600 or severe deficiency levels <100.

Discussion Serum MBL forms part of the complement activation and innate immune system and protects the lung from infection by organisms that bind mannose sugar (eg, strep, staph, yeasts, P.Jiveci). MBL deficiency gives an opsonisation defect with reduced phagocytosis by alveolar macrophages. Blood levels are genetically determined, with UK population data showing:

  • 12% severe deficiency <100 pg/ml,

  • 34% moderate deficiency 100–600 pg/ml,

  • 54% normal < 650 pg/ml.

Serum levels relate to polymorphisms of the MBL2 genes. χ2 analysis of frequency distribution showed no differences for HC, COPD & IPF>50 years. TB&Sarcoid had higher frequencies of normal MBL levels compared with HC (p=0.001 and 0.024 respectively). IPF <50 & IPF& FH showed higher frequencies of moderate and severe deficiency compared with HC and all other groups (p=0.001 and 0.001 respectively).

The literature shows MBL to consistently have interesting and important central roles in lung defenses via effects on complement, apoptosis and cytokines. Its observed deficiency in young IPF and those with a FH could be a genetic risk factor of relevance, explaining its early occurrence in deficiency and later occurrence in ‘sufficiency’, where it gives protection from insult or injury to the lung.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.