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 Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 29  |  Issue : 2  |  Page : 84-87

Anti-centriole antibody: An infectious or autoimmune process?


Department of Immunopathology, PGIMER, Chandigarh, India

Date of Web Publication9-Mar-2016

Correspondence Address:
Seema Chhabra
Room No 29, 4th Floor, Research Block A, Department of Immunopathology, PGIMER, Sector-12, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-6691.178274

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  Abstract 

Anti-centriolar pattern of staining by indirect immunofluorescence (IIF) on human epithelial type 2 (Hep2) cells is rarely observed, mostly in association with scleroderma and scleroderma-like connective tissue disorders. This paper describes four patients with anti-centriole antibody positivity along with a review of the available literature. In this retrospective study, a total of four cases whose serum showed the centriolar pattern on Hep2 cell lines during IIF examination were reviewed. The presence of anti-centriole antibody in the serum should herald the diagnosis of scleroderma spectrum; Raynaud's phenomenon and pulmonary arterial hypertension should be specifically looked for. In the absence of features of autoimmunity, patients should be screened for Mycoplasma infection.

Keywords: Autoimmunity, centriole, Mycoplasma, scleroderma


How to cite this article:
Saikia B, Kumar Y, Minz RW, Chhabra S. Anti-centriole antibody: An infectious or autoimmune process?. Indian J Allergy Asthma Immunol 2015;29:84-7

How to cite this URL:
Saikia B, Kumar Y, Minz RW, Chhabra S. Anti-centriole antibody: An infectious or autoimmune process?. Indian J Allergy Asthma Immunol [serial online] 2015 [cited 2019 Nov 22];29:84-7. Available from: http://www.ijaai.in/text.asp?2015/29/2/84/178274


  Introduction Top


Centrioles are cylindrical cell structures, composed mainly of tubulin and are involved in the organization of the mitotic spindle and completion of cytokinesis during cell division. First described by Brenner et al., anti-centriole antibodies are detected, albeit rarely, in patients with scleroderma and scleroderma-like connective tissue disorders. [1],[2],[3],[4],[5],[6] Osborn et al. reported isolated anti-centriole antibody positivity in a patient with systemic sclerosis, Raynaud's phenomena, sclerodactyly and pulmonary dysfunction. [1] Tuffanelli et al. reported anti-centriole antibodies in 4 of 80 patients with scleroderma, 1 with Raynaud's phenomena and 3 with systemic sclerosis. [2]

In this retrospective study, a total of four cases whose serum showed the centriolar pattern on human epithelial type 2 (Hep2) cell lines during indirect immunofluorescence (IIF) examination, were reviewed. The clinical details such as age, sex, and presenting complaints were noted from patients' case files, and the same was recorded along with their investigative work up test results. As part of screening, all these patients were investigated for any associated autoimmune disorder, and screening for ANA and ANCA was done. ANA line blot assay as well as cold agglutination testing for screening of Mycoplasma infection were also performed wherever sera was available.


  Case reports Top


Case 1

A 58-year-old female presented to the Neurology clinic with complaints of the excessive slowness of movement since 3 years, followed by behavioral disturbances and postural instability since 2½ years along with gait disturbances and frequent falls since 1 year. Apart from slowness of movement, she also complained of difficulty in initiating movements. She had behavioral disturbances in the form of apathy and anhedonia. She also had downward gaze paresis. Her hematological and biochemical profile was normal. A contrast-enhanced computerized tomography (CT) scan showed bilateral cerebral atrophy, with nigrostriatal pathway degeneration and midbrain atrophy. A possibility of Parkinsons plus syndrome with progressive supranuclear palsy was kept, and the patient started on a combination of carbidopa 25 mg and levodopa 100 mg, qid following which her symptoms improved.

Case 2

A 12-year-old female presented with nephrotic range proteinuria, swelling of face and limbs and itchy skin lesions in the form of erythematous rashes over face and trunk since 4 months. Urine examination showed 3+ proteinuria and Escherichia coli more than 10 5 /ml with no RBCs. Prothrombin and activated partial thromboplastin times were prolonged. Serum creatinine and urea levels were within normal limits. At the same time, when serum sample for ANA testing was being taken, a renal biopsy was also performed. Renal biopsy showed mesangioproliferative immune complex-mediated glomerulonephritis possibly IgA nephropathy, lupus nephritis or C1q nephropathy. Tissue submitted for direct immunofluorescence microscopy did not show any glomerulus so immunofluorescence was performed on paraffin section, but found to be negative for IgG, IgA, IgM, C3, kappa, lambda, and C1q. In the absence of diffuse immune complex deposits and normal C3 levels, lupus nephritis appeared unlikely. Electron microscopy showed focal effacement of podocyte foot processes with the presence of few sub-epithelial and mesangial deposits. No skin biopsy was performed. Hence, SLE was concluded a most probable diagnosis in this case.

Case 3

A 25-year-old female presented with recurrent nonhealing ulcers on lateral aspect of feet, hands with severe pain and purulent discharge, bluish discoloration of toes, recurrent oral ulcers, photosensitivity, alopecia, and numbness with parasthesias in both lower limbs below knee since 1½ year as well as gangrene right thumb since 15 days. On clinical examination, power in both upper and lower limbs was found to be normal while sensations to fine touch were found to be reduced to 20%. Nerve conduction study suggested asymmetrical sensorimotor axonal polyneuropathy. Anti-ds-DNA antibodies, anti-cardiolipin antibodies, IgG and M anti-phospholipid antibodies and lupus anticoagulant were negative. Patients' serum showed normal C-reactive protein levels. Serum fibrinogen and lactate dehydrogenase levels were normal while D-dimer test was positive. The patient was also negative for viral markers including HIV, anti-HCV antibodies and hepatitis B surface antigen. The rest of the biochemical parameters were within normal limits. Skin biopsy showed nonspecific inflammation on routine histopathology while direct immunofluorescence microscopy showed positivity with IgG and C 3 in upper dermal blood vessels based on which, a diagnosis of systemic vasculitis was suggested.

Case 4

A 66-year-old lady presented with features of Raynaud's phenomenon of 5 years duration and amputation of digits of both hands. She also complained of increasing dyspnea on exertion and fatigue since 2 months. On examination, pulmonary artery pressure was found to be more than 25 mmHg and so labeled as a case of pulmonary arterial hypertension.

IIF of the patients' serum on Hep2 cells in all four cases revealed a strong isolated anti-centriole antibody pattern of staining [Figure 1]. The anti-centriole antibody positivity was seen as one or more discrete dots within the cytoplasm close to the nuclear margin. IIF with "O positive" neutrophil as a substrate was, done for ANCA screening, and showed single discrete dots in the cytoplasm of all the neutrophils. A closer examination of these dots revealed that most of these dots in many neutrophils, as well as Hep2 cells, were a conglomerate of two discrete dots, which in some cells were better discerned. An ANA line blot assay performed in Case 4 showed 3 + positivity for SS-A and Ro-52. ANCA by IIF as well as ELISA for PR3 and MPO was negative in all four cases. Cold agglutination test for Mycoplasma infection was performed in Cases 1 and 4 where sera were available and showed a titer of 1:8 (significant titer being 1:32).
Figure 1: Indirect immunofluorescence on human epithelial type 2 cells from Case 1 showing (a) centriolar pattern of staining seen as discrete dots in the cytoplasm close to the nuclear margin, (b) centriolar dots appearing to be a conglomerate of two discrete dots in most of the cells, (c) centriolar staining in a mitotic figure, (d) indirect immunofluorescence on ANCA spots from Case 1 showing centriolar staining in neutrophils

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  Discussion Top


Raynaud's phenomenon seems to be a dominant feature in many patients with anti-centriole antibodies. The association of pulmonary hypertension with anti-centrole antibodies was first documented by Hayakawa et al. [7] Case 4 in our series had severe pulmonary arterial hypertension. It is, therefore, likely that these antibodies directed against cell components involved with cell division viz., centromeres and centrioles cause vascular damage resulting in Raynaud's phenomenon, digital ulceration, and pulmonary hypertension.

It has been observed in a murine model that Mycoplasma infection triggers the development of anti-centrosome antibodies, more specifically anti-centrosome IgG, and this centrosome autoreactivity could be prevented by antibiotic treatment. [8] Interestingly, neurologic manifestations, including late-onset encephalitis, myelitis, cerebellar dysfunction, Guillain-Barré Syndrome, cranial and peripheral neuropathies and striatal necrosis are observed in Mycoplasma infection. [9] Case 1 in our series had presented with predominant CNS manifestations and Parkinsonian features along with CT evidence of nigrostriatal pathway degeneration and midbrain atrophy without any other features to suggest systemic autoimmunity. Parkinsonian features including hypophonia, hypomimia, bradykinesia, and dystonia has been reported in association with Mycoplasma pneumonia infection, suggesting a probable link between anti-centriole antibodies, Mycoplasma infection and CNS manifestations. [10] Mycoplasma infection has also been associated with glomerulonephritis and the nephrotic syndrome, especially in children [11] and Case 2 in our series presented with nephrotic syndrome though the patient had features to suggest an autoimmune etiology. Hence, there seems to be two different pathogenetic mechanisms pertaining to the development of anti-centriole antibodies, one as a result of an infectious agent and the other as a part of autoimmunity and connective tissue disorders, exemplified by the later three cases in our series.

Being a retrospective analysis, we could not document Mycoplasma infection by sophisticated tools like PCR and ELISA-based assays in our patients because of the lack of appropriate blood samples and the cold agglutination test employed here in two cases is a very nonspecific test. The purpose of this study is to sensitize the clinicians and pathologists to investigate patients with anti-centriole antibodies for Mycoplasma, especially in the absence of salient features of autoimmune diseases [Figure 2].
Figure 2 : Venn diagram to show the overlap between autoimmunity, Mycoplasma infection and anticentriole antibodies

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Thus, we have noted the presence of anti-centriole antibodies and described the clinical context in which it is detectable. We propose that if the association between the presence of anti-centriolar antibodies and Mycoplasma can be proven by molecular techniques in Case 1 showing Parkinsonian features along with seroreactivity for Mycoplasma then probably this will further strengthen the theory of "infectious agents triggering autoimmune diseases."

Acknowledgment

Sincere acknowledgements to Mrs. Ranjeet Bhardwaj for providing all the technical support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Osborn TG, Patel NJ, Ross SC, Bauer NE. Antinuclear antibody staining only centrioles in a patient with scleroderma. N Engl J Med 1982;307:253-4.  Back to cited text no. 1
[PUBMED]    
2.
Tuffanelli DL, McKeon F, Kleinsmith DM, Burnham TK, Kirschner M. Anticentromere and anticentriole antibodies in the scleroderma spectrum. Arch Dermatol 1983;119:560-6.  Back to cited text no. 2
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3.
Moroi Y, Murata I, Takeuchi A, Kamatani N, Tanimoto K, Yokohari R. Human anticentriole autoantibody in patients with scleroderma and Raynaud′s phenomenon. Clin Immunol Immunopathol 1983;29:381-90.  Back to cited text no. 3
[PUBMED]    
4.
Gentric A, Blaschek MA, Le Noach JF, Johanet C, Jouquan J, Lamour A, et al. Serological arguments for classifying Raynaud′s phenomenon as idiopathic. J Rheumatol 1990;17:1177-81.  Back to cited text no. 4
    
5.
Rattner JB, Martin L, Waisman DM, Johnstone SA, Fritzler MJ. Autoantibodies to the centrosome (centriole) react with determinants present in the glycolytic enzyme enolase. J Immunol 1991;146:2341-4.  Back to cited text no. 5
    
6.
Sato S, Fujimoto M, Ihn H, Takehara K. Antibodies to centromere and centriole in scleroderma spectrum disorders. Dermatology 1994;189:23-6.  Back to cited text no. 6
    
7.
Hayakawa I, Sato S, Hasegawa M, Echigo T, Takehara K. A case of scleroderma spectrum disorder with anticentriole antibody and pulmonary hypertension. Clin Rheumatol 2004;23:266-8.  Back to cited text no. 7
    
8.
Catrinel GI. Autoantibodies to Centrosomes are Diagnostic of Human Scleroderma and can be Induced by Experimental Mycoplasma Infection in Mice: A Dissertation". University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 76; 2002. Available from: http://www.escholarship.umassmed.edu/gsbs_diss/76. [Last cited on 2014 Jun 26].  Back to cited text no. 8
    
9.
Narita M. Pathogenesis of neurologic manifestations of Mycoplasma pneumonia infection. Pediatr Neurol 2009;41:159-66.  Back to cited text no. 9
    
10.
Cimolai N, Mah D, Roland E. Anticentriolar autoantibodies in children with central nervous system manifestations of Mycoplasma pneumoniae infection. J Neurol Neurosurg Psychiatry 1994;57:638-9.  Back to cited text no. 10
    
11.
Saïd MH, Layani MP, Colon S, Faraj G, Glastre C, Cochat P. Mycoplasma pneumoniae-associated nephritis in children. Pediatr Nephrol 1999;13:39-44.  Back to cited text no. 11
    


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