A rare cause of anti-nucleolar (Th/To) antibody seropositivity in interstitial pneumonia with autoimmune features/undifferentiated connective tissue disease

Chhabra Seema1, Dhir Varun2, Dhooria Sahajal3, Walker R Minz1
1 Department of Immunopatholgy, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Internal Medicine (Rheumatology Unit), Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Click here for correspondence address and email

Date of Submission12-May-2022Date of Acceptance02-May-2023Date of Web Publication09-Jun-2023 How to cite this article:
Seema C, Varun D, Sahajal D, Minz WR. A rare cause of anti-nucleolar (Th/To) antibody seropositivity in interstitial pneumonia with autoimmune features/undifferentiated connective tissue disease. Indian J Pathol Microbiol 2023;66:676-7
How to cite this URL:
Seema C, Varun D, Sahajal D, Minz WR. A rare cause of anti-nucleolar (Th/To) antibody seropositivity in interstitial pneumonia with autoimmune features/undifferentiated connective tissue disease. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Jul 30];66:676-7. Available from: https://www.ijpmonline.org/text.asp?2023/66/3/676/379165

Dear Editor,

A 64-year-old woman presented with a complaint of cough and wheeze for 7 months. She had a prior history of hand joint arthritis, which lasted for a few months and Raynaud's in two fingers. High-resolution computed tomography, HRCT [Figure 1]a, thorax showed asymmetrical subpleural interstitial thickenings in right upper lobe and bilateral lower lobes consistent with early interstitial lung disease-fibrotic nonspecific interstitial pneumonia (ILD-NSIP). Her pulmonary function test reports were within normal limits for age and gender. She does not have any history and/or clinical features of sclerodactyly, calcinosis cutis, digital pitting scar, telangiectasias, cutaneous form of systemic sclerosis (SSc), pericarditis, muscle damage, and upper and lower digestive signs including gastro-oesophageal reflux.

Figure 1: (a). Cut-out image of HRCT-thorax showing mild basal interstitial thickening; (b). IIF photomicrograph of HEp-2 slide showing nucleolar and fine speckled nucleoplasm staining. (×400); (c): Systemic sclerosis Immunoblot (13 antigens) showing 3+ positivity for Th/To

Click here to view

HEp-2 indirect immunofluorescence assay (IIFA) (Innovalite, 1053386) displayed 3+ nucleolar immunofluorescence pattern [Figure 1]b of antinuclear antibodies (ANAs). With a history of cough and wheeze consistent with ILD, and the presence of nucleolar ANA (that suggests anti-U3 RNP, anti-Th/To, anti-NOR 90, and anti-PM/Scl, which are the most common antibodies directed against nucleolar antigens), a SSc immunoblot (Euroimmun AG, Lübeck, Germany) for 13 different autoantibody specificities was planned to determine the antigenic target. It showed 3+ anti-Th/To antibodies (anti-Th/To) positivity, while other SSc classical autoantibodies (anticentromere, anti-RNA polymerase III, and anti-topoisomerase I/Scl-70) were negative as shown in [Figure 1]c.

Among the antibodies described in SSc, anti-Th/To antibodies are rare with an estimated mean frequency of 3.4% of all SSc patients worldwide.[1] They carry a high specificity of around 98% for the diagnosis of SSc and are important in SSc patients who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays.[2] However, there have also been reports of Th/To being found in patients who cannot be classified as SSc but may have ILD, Raynaud's, etc.[3]

Th/To antigens are situated in the nucleolus of the cell nucleus and recognize enzymes involved in RNA processing, that is, ribonuclease mitochondrial RNA processing complex (RNase MRP)/Th and ribonuclease P (RNase P)/To. Now at least nine individual proteins linked with these complexes have been characterized and described as targets of autoantibodies in SSc. Recently, the presence of Th/To complex autoantibodies in SSc has shown negative association with cancer and positive association with a clinical phenotype most notable for pulmonary involvement.[4]

The diagnosis of the index patient fulfils criteria for both undifferentiated connective tissue disease (UCTD) and interstitial pneumonia with autoimmune features.[5] Our case of a lady with UCTD was managed symptomatically for her complaints and remains on follow-up. It highlights an unusual, rare, and exclusive occurrence of this nucleolar antibody the index case. We believe this is the first report of this autoantibody from the Indian subcontinent, and highlights that apart from limited scleroderma, it can be associated with UCTD/IPAF.

Acknowledgement

We would also like to thank Ms. Ranjeet for technical assistance in carrying out all the diagnostic assays including indirect immunofluorescence, ELISAs, and blots for the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.Mahler M, Satoh M, Hudson M, Baron M, Chan JY, Chan EK, et al. Autoantibodies to the Rpp25 component of the Th/To complex are the most common antibodies in patients with systemic sclerosis without antibodies detectable by widely available commercial tests. J Rheumatol 2014;41:1334-43.

2.Muller R, Benyamine A, Bertin D, Harlé JR, Kaplanski G, Mazodier K, et al. Characteristics of systemic sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review. Rev Med Interne 2020;41:440-45.

3.Kuwana M, Kimura K, Hirakata M, Kawakami Y, Ikeda Y. Differences in autoantibody response to Th/To between systemic sclerosis and other autoimmune diseases. Ann Rheum Dis 2002;61:842-6.

4.Mecoli CA, Adler BL, Yang Q, Hummers LK, Rosen A, Casciola-Rosen L, Shah AA. Cancer in systemic sclerosis: Analysis of antibodies against components of the Th/To complex. Arthritis Rheumatol 2021;73:315-23.