The secondary nature of ciliary (dis)orientation in secondary and primary ciliary dyskinesia.

OBJECTIVE

Ciliary orientation (COR) is an important parameter of mucociliary clearance and ciliary disorientation has been reported in cases of acquired abnormalities [secondary ciliary dyskinesia (SCD)] and in a very few cases as the single abnormality in primary ciliary dyskinesia (PCD). The etiology, pathogenesis, consequences and relevance of ciliary (dis)orientation are still unclear.

MATERIAL AND

METHODS

To elucidate the primary or secondary nature of ciliary (dis)orientation, COR was measured in 179 non-PCD and 59 PCD patients. COR was measured in biopsies and after ciliogenesis in culture and was correlated with a number of functional and ultrastructural parameters. COR was defined as the SD of the angles of lines through the central pair of microtubules using transmission electron microscopy. Internationally accepted normal values for COR are < or = 20 degrees; COR values of 20-35 degrees indicate increased disorientation; and COR values > 35 degrees represent a random orientation.

RESULTS

For non-PCD biopsies, COR increased with increasing SCD, from 15 +/- 7 degrees (n = 54) for normal (< 5%) SCD to 28 +/- 8 degrees (n = 16) for severe (> 25%) SCD. No correlation was found between COR and ciliary beat frequency. However, increased COR values (28 +/- 8 degrees) were found for immotility (n = 8), compared to (coordinated) ciliary activity (19 +/- 9 degrees) (n = 121). After ciliogenesis no ultrastructural abnormalities were found and COR was normal (13 +/- 5 degrees; n = 308). COR can therefore be considered to be secondary in non-PCD and correlates with SCD percentage and ciliary motility. In biopsies from PCD patients with dynein deficiency and with normal ultrastructure, COR was increased, to 28 +/- 11 degrees (n = 32) and 21 +/- 7 degrees (n = 15), respectively, and in cases with central pair abnormalities COR was random (38 +/- 11 degrees; n = 12). After ciliogenesis COR remained random in the PCD group with central pair abnormalities (38 +/- 9 degrees; n = 15), and was increased in the PCD groups with dynein deficiency (24 +/- 10 degrees; n = 35) and normal ultrastructure (25 +/- 8 degrees; n = 17). Ciliary disorientation was never found as the single abnormality.

CONCLUSION

COR can be considered to be secondary in PCD. Both ciliary (im)motility and SCD percentage contribute to COR.