Background
Methods
Search strategy
Inclusion criteria
Exclusion criteria
Data extraction
Statistical analysis and methodological quality assessment
Results
Studies included
First author/Year (Ref.) | Country | Molecular technique | Sarcoidosis patients | Non-sarcoidosis controls | OR (95% CI) | ||
---|---|---|---|---|---|---|---|
n/N | Type of microorganisms | n/N | Type of microorganisms | ||||
Bocart, 1992 [23] | France | PCR of 65 kDa mycobacterial antigen and IS6110 | 2/22 | MTBC | 0/22 | - | 5.49 (0.25–121.18) |
Hofland, 2014 [20] | Netherlands | NAAT for Mycobacteria and Culture | 0/32 | - | 2/86 | 1 MTBC, 1NTM | 0.52 (0.02–11.13) |
Robinson, 2013 [24] | USA | PCR for 16S rDNA, hsp65 and rpoB | 2/30 | NTM | 1/30 | NTM | 2.07 (0.18–24.15) |
Oswald-Richter, 2012 [25] | USA | MALDI-IMS for ESAT-6 | 5/15 | Mycobacterium spp | 0/4 | - | 4.71 (0.21–104.49) |
Svendsen, 2011 [26] | Denmark | BD ProbeTec IS6110 amplification | 1/52 | MTBC | 0/50 | - | 2.94 (0.12–73.93) |
Mootha, 2010 [27] | India | PCR of 65 kDa mycobacterial antigen and IS6110 | 13/27 | 10 MTBC, 3 NTM | 2/40 | NTM | 17.64 (3.53–88.25) |
Zhou, 2008 [28] | China | Real-time PCR of IS986 and human β-blobin gene | 20/104 | MTBC | 7/55 | MTBC | 1.63 (0.64–4.14) |
Dubaniewicz, 2006 [29] | Poland | BD ProbeTec IS6110 amplification | 3/50 | MTBC | 0/10 | - | 1.55 (0.07–32.27) |
Fite, 2006 [30] | Spain | PCR of IS6110 and Southern blot hybridisation | 9/23 | MTBC | 1/23 | MTBC | 14.14 (1.61–124.11) |
Yasuhara, 2005 [31] | Japan | PCR of IS6110 | 0/6 | - | 0/6 | - | - |
Song, 2005 [32] | USA | PCR of MTB 16S rRNA | 6/16 | MTBC | 0/16 | - | 20.43 (1.04–401.67) |
Marcoval, 2005 [33] | Spain | NAAT for rRNA of MTBC | 0/35 | - | 0/39 | _ | - |
Yu-Yun Lee, 2002 [34] | Taiwan | Nested PCR for mycobacterial hsp65 DNA | 7/21 | NTM | 0/16 | - | 17.07 (0.89–325.59) |
Drake, 2002 [21] | USA | PCR of 16S rRNA, rpoB and IS6110 | 15/25 | 11 MTBC, 3 NTM, 1 both | 0/25 | _ | 75.29 (4.12–1377.06) |
Gazouli, 2002 [22] | Greece | PCR of IS6110/IS1245/IS900/IS901, 16S rRNA, MPB64 and mtp40 | 33/46 | MTBC | 0/20 | - | 101.74 (5.74–1804.62) |
Eish, 2002 [35] | Japan | PCR of IS6110/IS900 | 5/108 | MTBC | 2/86 | MTBC | 2.04 (0.39–10.78) |
Klemen, 2000 [36] | Austria | PCR of IS6110 and mycobacterial chaperonin | 3/4 | NTM | 0/39 | _ | 184.33 (6.26–5425.48) |
Li, 1999 [37] | USA | PCR of 65 kDa mycobacterialantigen and RFLP analysis | 16/20 | 2 MTBC, 14 NTM | 0/20 | _ | 150.33 (7.54–2997.83) |
Ishige, 1999 [38] | Japan | PCR of IS6110 | 3/15 | MTBC | 1/15 | MTBC | 3.50 (0.32–38.23) |
Wilsher, 1998 [39] | NZ | PCR of IS6110, nested PCR to amplify 85 bp sequence within the 123 bp product | 0/31 | _ | 0/10 | - | - |
Di Alberti, 1997 [40] | Italy | Heminested PCR for 16S rRNA | 17/38 | 4 NTM, 13 Mycobacterium spp | 39/113 | 39 Mycobacterium spp | 1.54 (0.73–3.24) |
Vokurka, 1997 [41] | France | PCR of IS6110 and DR region | 0/15 | _ | 0/27 | _ | - |
Ozcelik, 1997 [42] | Turkey | PCR of IS6110 | 5/11 | MTBC | 2/15 | MTBC | 5.42 (0.81-36.36) |
Popper, 1997 [43] | Austria | PCR of 65 kDa mycobacterial antigen and IS6110 | 11/35 | NTM | 0/39 | - | 37.08 (2.09–657.90) |
El-Zaatari, 1996 [44] | USA | PCR of IS900/IS902, MAC-specific PCR assay and Western blot | 7/7 | NTM | 13/38 | NTM | 28.33 (1.50–534.74) |
Fidler, 1993 [45] | UK | PCR of 65 kDa mycobacterial antigen and IS6110 | 7/16 | MTBC | 1/16 | MTBC | 11.67 (1.23–110.95) |
Thakker, 1992 [46] | UK | PCR of groEL | 1/14 | MTBC | 1/11 | MTBC | 0.77 (0.04–13.87) |
Gerdes, 1992 [47] | Germany | PCR of 16S rDNA | 0/14 | - | 0/10 | - | - |
Mitchell, 1992 [48] | UK | Mycobacterial rRNA detection by liquid phase hybridisation | 5/5 | MTBC | 0/5 | - | 121 (2.02–7259.18) |
Saboor, 1992 [49] | UK | PCR of IS986/IS6110 and groEL | 14/20 | 10 MTBC, 4 NTM | 5/22 | 3 MTBC, 2 NTM | 7.93 (1.99–31.59) |
Lisby, 1993 [50] | Denmark | Nested PCR for IS900 | 0/18 | - | 0/18 | - | - |
Grosser, 1999 [51] | Germany | PCR of IS986/IS6110 | 35/65 | MTBC | 1/34 | MTBC | 38.50 (4.96–298.57) |
Vago, 1998 [52] | Italy | PCR of IS6110 | 2/30 | MTBC | 0/17 | - | 3.07 (0.14–67.75) |
Richter, 1996 [53] | Germany | PCR of mycobacterial 16S rDNA | 1/24 | MTBC | 3/57 | MTBC | 0.78 (0.08–7.93) |
Ghossein, 1994 [54] | USA | PCR of 65 kDa mycobacterial antigen | 0/10 | - | 0/10 | - | - |
Cannone, 1997 [55] | Italy | PCR of IS6110 | 2/30 | MTBC | 0/10 | - | 1.84 (0.08–41.62) |
First author/Year (Ref.) | Country | Molecular technique | Sarcoidosis | Controls | OR (95% CI) |
---|---|---|---|---|---|
n/N | n/N | ||||
Robinson, 2013 [24] | USA | PCR for bacterial 16S rDNA | 7/30 | 1/30 | 8.83 (1.01–76.96) |
Oswald-Richter, 2012 [25] | USA | MALDI-IMS for propionibacterial proteins | 7/15 | 1/4 | 2.63 (0.22–31.35) |
Yasuhara, 2005 [31] | Japan | PCR for 16S rRNA | 2/6 | 0/6 | 7.22 (0.28–189.19) |
Gazouli, 2002 [22] | Greece | PCR for 16S rRNA | 0/46 | 0/20 | - |
Eish, 2002 [35] | Japan | PCR for 16S rRNA | 93/108 | 25/86 | 15.13 (7.39–30.99) |
Ishige, 1999 [38] | Japan | Quantitative PCR for 16S rRNA | 12/15 | 3/15 | 16 (2.67–95.75) |
Negi, 2012 [56] | Japan | Immunohistochemical methods (PAG and TIG antibodies) and western blot | 149/196 | 0/79 | 500.43 (30.44–8226.20) |
Yamada, 2002 [57] | Japan | Quantitative real-time PCR for 16S rRNA | 8/9 | 2/9 | 28 (2.07–379.25) |
Eishi, 1994 [58] | Japan | PCR for P. acnes DNA | 36/39 | 12/29 | 17 (4.23–68.28) |
Abe, 1984 [19] | Japan | Isolation of P acnes in culture | 31/40 | 38/180 | 12.87 (5.65–29.34) |
Hiramatsu, 2003 [59] | Japan | Nested PCR for 16S rRNA | 21/30 | 7/30 | 7.67 (2.42–24.24) |
First author/Year (Ref.) | Country | Molecular technique | Patients | Controls | OR (95% CI) |
---|---|---|---|---|---|
n/N | n/N | ||||
Knoell, 2005 [60] | USA | PCR for HHV-8 DNA | 0/8 | 0/8 | - |
Gazouli, 2002 [22] | Greece | PCR for HHV-8 DNA | 0/46 | 0/20 | - |
Fredricks, 2002 [61] | USA | PCR for HHV-8 ORF 26 DNA | 0/18 | 0/4 | - |
Maeda, 2000 [62] | Japan | Hemi-nested PCR for HHV-8 DNA | 4/119 | 4/120 | 1.01 (0.25–4.13) |
Sugaya, 1999 [63] | Japan | Nested PCR for HHV-8 ORF 26 DNA | 0/12 | 1/1 | 0.01 (0.00–0.95) |
Bélec, 1998 [64] | France | Nested PCR for HHV-8 ORF 25/26 DNA | 0/14 | 2/17 | 0.21 (0.01–4.84) |
Di Alberti, 1997 [40] | Italy | Nested PCR for HHV-8 ORF 26 DNA and Heminested PCR for HHV-8 ORF 25 DNA | 38/39 | 6/113 | 677.67 (79.01–5812.52) |
First author/Year (Ref.) | Country | Molecular Technique | Sarcoidosis | Controls | OR (95% CI) | ||
---|---|---|---|---|---|---|---|
n/N | Type of microorganism | n/N | Type of microorganism | ||||
Derler, 2009 [4] | Austria | Focus-floating microscopy and Borrelia-specific PCR DNA | 13/35 | Borrelia sp. | 1/61 | Borrelia sp. | 35.45 (4.38–287.16) |
Ishihara, 1998 [65] | Japan | Dot-blot analysis (Dotblot Borrelia Kit) | 15/46 | Borrelia sp. | 2/100 | Borrelia sp. | 23.71 (5.14–109.46) |
Martens, 1997 [66] | Germany | Western blot for Borrelia burgdorferi | 1/60 | Borrelia burgdorferi | 27/1000 | Borrelia burdorferi | 0.61 (0.08–4.57) |
Lian, 1995 [67] | China | PCR for Borrelia burgdorferi DNA | 6/49 | Borrelia burgdorferi | 2/28 | Borrelia burgdorferi | 1.81 (0.34–9.66) |
Xu, 1996 [68] | China | In situ PCR for Borrelia burgdorferi DNA | 0/23 | - | 0/23 | - | - |
Ishihara, 1996 [69] | Japan | Elisa and Dot-blot analysis for Borrelia sp. | 1/38 | Borrelia sp. | 1/80 | Borrelia sp. | 2.14 (0.13–35.08) |
Meta-analysis
Mycobacteria (Table 1)
P. acnes (Table 2)
Borrelia and HHV-8 (Tables 3 and 4)
Evaluation of publication bias
Sensitivity and subgroup analysis
Subgroup analysis
No. of studies | OR (95%CI) | P-value heterogeneity | I2 (%) | |
---|---|---|---|---|
Subgroup analysis | ||||
1 - Geographical region | ||||
Europe | 22 | 6.92 (3.05, 15.71) | 0.004 | 53.8 |
USA | 7 | 18.21 (4.64, 71.53) | 0.238 | 26.2 |
Asia | 7 | 4.09 (1.38, 12.12) | 0.093 | 49.8 |
2 - Publication year | ||||
< 2000 | 20 | 6.63 (2.84, 15.51) | 0.006 | 54.2 |
> =2000 | 16 | 8.40 (3.31, 21.31) | 0.012 | 53 |
3 – Type of study | ||||
Prospective | 10 | 11.91 (4.94, 28.69) | 0.743 | 0.0 |
Retrospective | 26 | 6.41 (3.14, 13.09) | 0.001 | 57.1 |
4 - Molecular technique | ||||
PCR | 29 | 7.04 (3.57, 13.89) | 0.000 | 58.8 |
Hybridization | 2 | 37.81 (3.40, 420.43) | 0.484 | 0.0 |
Protein analysis | 2 | 12.12 (1.44, 102.20) | 0.408 | 0.0 |
BD ProbeTec | 2 | 2.09 (0.23, 19.10) | 0.776 | 0.0 |
Culture | 1 | 0.52 (0.02, 11.13) | - | - |
Sensitivity analysis | ||||
1 - Biological samples | ||||
Only lymph nodes | 11 | 3.82 (1.53, 9.49) | 0.384 | 4.0 |
Only lung | 5 | 2.93 (1.09, 7.86) | 0.098 | 56.9 |
Only skin | 2 | 11.58 (0.06, 2016.91) | 0.021 | 81.3 |
2 – Incidence of tuberculosis | ||||
Only countries with low burden of TB | 33 | 4.33 (2.06, 9.10) | 0.042 | 45.7 |