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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Interstitial lung disease &#40;ILD&#41; are a large and heterogeneous group of diseases with known and unknown causes&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> In some cases the clinical course of ILD is progressive and does not always require the same therapeutic approach&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#44;3</span></a> ILD is a frequent cause of major morbidity and mortality in multi-system disorders&#44; especially in patients with connective tissue diseases &#40;CTDs&#41;&#44; with an estimated prevalence of 30&#46;2 cases per 100&#44;000&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> One of the hallmarks of CTD is the presence of autoantibodies &#40;Ab&#41;&#44; being the elevated titration of antinuclear antibodies &#40;ANA&#41; or the presence of autoantibodies against extractable nuclear antigens &#40;ENA&#41; useful as serological biomarkers of these kind of diseases&#46; ILD usually occurs concomitantly or after the onset of CTDs&#44; but in some patients ILD may be the first manifestation of an underlying CTD&#46; Moreover a percentage of ILD patients have features of an autoimmune process in the absence of a defined CTD&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> But it is important to highlight that the absence of ENA or other specific Ab in blood does not exclude the existence of an underlying CTD&#46; It seems reasonable to think that the study of Ab presence in biological samples other than serum could improve their diagnostic profitability&#46; A study carried out in 56 patients with pleural effusion showed that an ANA titer in pleural fluid<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#47;160 presented a sensitivity and specificity of 91&#46;67&#37; and 83&#46;3&#37; respectively for the diagnosis of lupus pleuritis compared to other causes of pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> However&#44; studies that have attempted to associate the ratio of pleural fluid ANA&#47;serum ANA show conflicting results&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">7&#8211;9</span></a> In addition the presence of ANA in pleural fluid has been also found in other pathologies like neoplasms&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Bronchoalveolar lavage &#40;BAL&#41; is useful to study different lung diseases and some authors have shown its prognostic value in some CTD-ILD as well as in the detection of their complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11&#8211;13</span></a> Currently BAL analysis in CTDs has been focused basically on the determination of different cellular products&#44; such as inflammatory mediators or biomarkers of cell damage&#46; But it is also possible to determine immunoglobulins in BAL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> This fact is particularly interesting in CTDs because these patients usually present increased numbers of cells that can produce Ab&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Salvador-Corres et al&#46; analyzed the presence of different ENA in BAL samples from 155 patients with suspected ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Interestingly they found several ENA Ab in 19 patients&#44; 7 of them having more than one ENA&#46; It is also noteworthy that after the analysis of Ab in BAL&#44; the percentage of patients categorized as CTD-ILD or IPAF increased from 23&#37; to 39&#46;5&#37; of the patients&#44; showing the potential usefulness of ENA determination in bronchoalveolar fluid&#46; Undoubtedly this finding may have consequences in the approachment of the study of these patients&#46; Another remarkable result of BAL analysis revealed that in 7 patients &#40;37&#37;&#41; ENAs found in BAL were not detected in the serum of the same patients&#44; being ENA positive in BAL and negative in the serum from 3 of them&#46; This finding also may be very important in our patients with CTD-ILD due to the different prognostic implications caused by the presence of several Ab together&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study of ENA in BAL of patients with suspected CTD-ILD has not been addressed before and&#44; according to these findings&#44; it could expand the diagnostic sensitivity in non-filiated ILD&#46; However&#44; despite being an interesting line of research&#44; additional studies are needed to validate the usefulness of determining CTDs&#8217; specific Ab in BAL&#46; First&#44; it is important to establish the pathogenic role of these antibodies in patients who only present ENA in BAL and not in blood test&#46; It is known that the presence specific CTD autoantibodies is not sufficient to diagnose as autoimmune disease&#46; In this way&#44; when Salvador-Corres et al&#46; compared the clinical and pulmonary functional test findings of CTD patients with and without ENA in BAL&#44; they did not find relevant differences&#46; The follow-up of these groups of patients can help to clarify questions and to reveal the diagnostic and prognostic role that ENA in BAL can play in this group of patients&#46; Another important point is that authors did not study all Ab associated with CTD-ILD and we do not know whether other Ab in BAL could be comparable&#46; For example&#44; the technique of determining antibodies against neutrophil cytoplasm &#40;ANCA&#41; and its specificities is not globally standardized&#46; Finally&#44; we cannot guarantee that the secretion of these antibodies has been in situ and their presence is rather due to the damage of the alveolo-capillary membrane as a result of ILD&#46; These and another uknowns need to be clarified taking into consideration that BAL is an invasive procedure&#46; Nevertheless&#44; the authors certainly opened an interesting approach to study of CTDs Ab in BAL deeply&#46; Future works in this line could validate the usefulness of this technique in the management of CTD-ILD&#46;</p></span>"
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Editorial
Autoimmunity in the Study of Interstitial Lung Disease: Are Serological Test Enough?
Ivan Castellvía,
Corresponding author
icastellvi@santpau.cat

Corresponding author.
, Silvia Vidalb, Claudia Valenzuelac
a Department of Rheumatology and Systemic Autoimmune Diseases, Hospital Universitari de la Santa Creu I Sant Pau, Barcelona, Spain
b Department of Immunology, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain
c Department of Pneumology, Hospital Universitario de la Princesa, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Interstitial lung disease &#40;ILD&#41; are a large and heterogeneous group of diseases with known and unknown causes&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> In some cases the clinical course of ILD is progressive and does not always require the same therapeutic approach&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#44;3</span></a> ILD is a frequent cause of major morbidity and mortality in multi-system disorders&#44; especially in patients with connective tissue diseases &#40;CTDs&#41;&#44; with an estimated prevalence of 30&#46;2 cases per 100&#44;000&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> One of the hallmarks of CTD is the presence of autoantibodies &#40;Ab&#41;&#44; being the elevated titration of antinuclear antibodies &#40;ANA&#41; or the presence of autoantibodies against extractable nuclear antigens &#40;ENA&#41; useful as serological biomarkers of these kind of diseases&#46; ILD usually occurs concomitantly or after the onset of CTDs&#44; but in some patients ILD may be the first manifestation of an underlying CTD&#46; Moreover a percentage of ILD patients have features of an autoimmune process in the absence of a defined CTD&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> But it is important to highlight that the absence of ENA or other specific Ab in blood does not exclude the existence of an underlying CTD&#46; It seems reasonable to think that the study of Ab presence in biological samples other than serum could improve their diagnostic profitability&#46; A study carried out in 56 patients with pleural effusion showed that an ANA titer in pleural fluid<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#47;160 presented a sensitivity and specificity of 91&#46;67&#37; and 83&#46;3&#37; respectively for the diagnosis of lupus pleuritis compared to other causes of pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> However&#44; studies that have attempted to associate the ratio of pleural fluid ANA&#47;serum ANA show conflicting results&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">7&#8211;9</span></a> In addition the presence of ANA in pleural fluid has been also found in other pathologies like neoplasms&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Bronchoalveolar lavage &#40;BAL&#41; is useful to study different lung diseases and some authors have shown its prognostic value in some CTD-ILD as well as in the detection of their complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11&#8211;13</span></a> Currently BAL analysis in CTDs has been focused basically on the determination of different cellular products&#44; such as inflammatory mediators or biomarkers of cell damage&#46; But it is also possible to determine immunoglobulins in BAL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> This fact is particularly interesting in CTDs because these patients usually present increased numbers of cells that can produce Ab&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Salvador-Corres et al&#46; analyzed the presence of different ENA in BAL samples from 155 patients with suspected ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Interestingly they found several ENA Ab in 19 patients&#44; 7 of them having more than one ENA&#46; It is also noteworthy that after the analysis of Ab in BAL&#44; the percentage of patients categorized as CTD-ILD or IPAF increased from 23&#37; to 39&#46;5&#37; of the patients&#44; showing the potential usefulness of ENA determination in bronchoalveolar fluid&#46; Undoubtedly this finding may have consequences in the approachment of the study of these patients&#46; Another remarkable result of BAL analysis revealed that in 7 patients &#40;37&#37;&#41; ENAs found in BAL were not detected in the serum of the same patients&#44; being ENA positive in BAL and negative in the serum from 3 of them&#46; This finding also may be very important in our patients with CTD-ILD due to the different prognostic implications caused by the presence of several Ab together&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study of ENA in BAL of patients with suspected CTD-ILD has not been addressed before and&#44; according to these findings&#44; it could expand the diagnostic sensitivity in non-filiated ILD&#46; However&#44; despite being an interesting line of research&#44; additional studies are needed to validate the usefulness of determining CTDs&#8217; specific Ab in BAL&#46; First&#44; it is important to establish the pathogenic role of these antibodies in patients who only present ENA in BAL and not in blood test&#46; It is known that the presence specific CTD autoantibodies is not sufficient to diagnose as autoimmune disease&#46; In this way&#44; when Salvador-Corres et al&#46; compared the clinical and pulmonary functional test findings of CTD patients with and without ENA in BAL&#44; they did not find relevant differences&#46; The follow-up of these groups of patients can help to clarify questions and to reveal the diagnostic and prognostic role that ENA in BAL can play in this group of patients&#46; Another important point is that authors did not study all Ab associated with CTD-ILD and we do not know whether other Ab in BAL could be comparable&#46; For example&#44; the technique of determining antibodies against neutrophil cytoplasm &#40;ANCA&#41; and its specificities is not globally standardized&#46; Finally&#44; we cannot guarantee that the secretion of these antibodies has been in situ and their presence is rather due to the damage of the alveolo-capillary membrane as a result of ILD&#46; These and another uknowns need to be clarified taking into consideration that BAL is an invasive procedure&#46; Nevertheless&#44; the authors certainly opened an interesting approach to study of CTDs Ab in BAL deeply&#46; Future works in this line could validate the usefulness of this technique in the management of CTD-ILD&#46;</p></span>"
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Article information
ISSN: 03002896
Original language: English
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