Polynucleotide Marker Genes and their Expression, for Diagnosis of Endotoxemia

A method for treating, preventing or inhibiting the development of an endotoxemia-related condition in a subject, the method comprising detecting aberrant expression of at least one endotoxemia marker gene in the subject, and administering to the subject an effective amount of an agent that treats or ameliorates the symptoms or reverses or inhibits the development of the endotoxemia-related condition in the subject, wherein the endotoxemia marker gene is expressed in cells of the immune system and is selected from the group consisting of:

• (a) a gene having a polynucleotide expression product comprising a nucleotide sequence that shares at least 50% sequence identity with the sequence set forth in any one of SEQ ID NO:
• 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 16, 17, 18, 19, 21, 23, 25, 26, 27, 29, 31, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 47, 49, 50, 52, 54, 56, 58, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 86, 88, 90, 92, 93, 94, 96, 98, 100, 101, 102, 103, 104, 106, 107, 109, 110, 111, 113, 114, 115, 117, 119, 121, 122, 123, 124, 125, 126, 128, 130, 132, 134, 136, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 158, 160, 162, 164, 166, 168, 169, 170, 172, 173, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 193, 194, 195, 197, 199, 201, 203, 205, 206, 207, 209, 210, 211, 212, 214, 215, 216, 218, 220, 222, 223, 224, 225, 227, 229, 231, 233, 235, 236, 237, 239, 240, 242, 244, 245, 246, 248, 250, 252, 254, 255, 257, 259 260, 262, 264, 266, 268, 269, 270, 271, 272, 274, 276, 278, 279, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 305, 306, 307, 309, 311, 312, 314, 315, 316, 318, 320 321, 323 or 325;
• or a complement thereof;
• (b) a gene having a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:
• 2, 8, 12, 14, 20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326;
• (c) a gene having a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 50% sequence similarity with at least a portion of the sequence set forth in SEQ ID NO:
• 2, 8, 12, 14, 20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326, wherein the portion comprises at least 15 contiguous amino acid residues of that sequence;
• and (d) a gene having a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under at least low stringency conditions.

An isolated endotoxemia marker polynucleotide selected from:

• (a) a polynucleotide comprising a nucleotide sequence that shares at least 50% sequence identity with the sequence set forth in any one of SEQ ID NO:
• 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 16, 17, 18, 19, 21, 23, 25, 26, 27, 29, 31, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 47, 49, 50, 52, 54, 56, 58, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 86, 88, 90, 92, 93, 94, 96, 98, 100, 101, 102, 103, 104, 106, 107, 109, 110, 111, 113, 114, 115, 117, 119, 121, 122, 123, 124, 125, 126, 128, 130, 132, 134, 136, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 158, 160, 162, 164, 166, 168, 169, 170, 172, 173, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 193, 194, 195, 197, 199, 201, 203, 205, 206, 207, 209, 210, 211, 212, 214, 215, 216, 218, 220, 222, 223, 224, 225, 227, 229, 231, 233, 235, 236, 237,239, 240, 242, 244, 245, 246, 248, 250, 252, 254, 255, 257, 259 260, 262, 264, 266, 268, 269, 270, 271, 272, 274, 276, 278, 279, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 305, 306, 307, 309, 311, 312, 314, 315, 316, 318, 320 321, 323 or 325, or a complement thereof, (b) a polynucleotide comprising a portion of the sequence set forth in any one of SEQ ID NO:
• 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 16, 17, 18, 19, 21, 23, 25, 26, 27, 29, 31, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 47, 49, 50, 52, 54, 56, 58, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 86, 88, 90, 92, 93, 94, 96, 98, 100, 101, 102, 103, 104, 106, 107, 109, 110, 111, 113, 114, 115, 117, 119, 121, 122, 123, 124, 125, 126, 128, 130, 132, 134, 136, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 158, 160, 162, 164, 166, 168, 169, 170, 172, 173, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 193, 194, 195, 197, 199, 201, 203, 205, 206, 207, 209, 210, 211, 212, 214, 215, 216, 218, 220, 222, 223, 224, 225, 227, 229, 231, 233, 235, 236, 237, 239, 240, 242, 244, 245, 246, 248, 250, 252, 254, 255, 257, 259 260, 262, 264, 266, 268, 269, 270, 271, 272, 274, 276, 278, 279, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 305, 306, 307, 309, 311, 312, 314, 315, 316, 318, 320 321, 323 or 325, or a complement thereof, wherein the portion comprises at least 15 contiguous nucleotides of that sequence or complement;
• (c) a polynucleotide that hybridizes to the sequence of (a) or (b) or a complement thereof, under at least low stringency conditions;
• and (d) a polynucleotide comprising a portion of any one of SEQ ID NO:
• 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 16, 17, 18, 19, 21, 23, 25,26, 27, 29, 31, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 47, 49, 50, 52, 54, 56, 58, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 86, 88, 90, 92, 93, 94, 96, 98, 100, 101, 102, 103, 104, 106, 107, 109, 110, 111, 113, 114, 115, 117, 119, 121, 122, 123, 124, 125, 126, 128, 130, 132, 134, 136, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 158, 160, 162, 164, 166, 168, 169, 170, 172, 173, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 193, 194, 195, 197, 199, 201, 203, 205, 206, 207, 209, 210, 211, 212, 214, 215, 216, 218, 220, 222, 223, 224, 225, 227, 229, 231, 233, 235, 236, 237, 239, 240, 242, 244, 245, 246, 248, 250, 252, 254, 255, 257, 259 260, 262, 264, 266, 268, 269, 270, 271, 272, 274, 276, 278, 279, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 305, 306, 307, 309, 311, 312, 314, 315, 316, 318, 320321, 323 or 325, or a complement thereof, wherein the portion comprises at least 15 contiguous nucleotides of that sequence or complement and hybridizes to a sequence of (a), (b) or (c), or a complement thereof, under at least low stringency conditions.

A method for diagnosing the presence of an endotoxemia-related condition in a test subject, comprising detecting in the test subject aberrant expression of at least one endotoxemia marker polynucleotide that is expressed in cells of the immune system and that is selected from the group consisting of:

• (a) a polynucleotide comprising a nucleotide sequence that shares at least 50% sequence identity with the sequence set forth in any one of SEQ ID NO:
• 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 16, 17, 18, 19, 21, 23, 25, 26, 27, 29, 31, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 47, 49, 50, 52, 54, 56, 58, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 86, 88, 90, 92, 93, 94, 96, 98, 100, 101, 102, 103, 104, 106, 107, 109, 110, 111, 113, 114, 115, 117, 119, 121, 122, 123, 124, 125, 126, 128, 130, 132, 134, 136, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 158, 160, 162, 164, 166, 168, 169, 170, 172, 173, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 193, 194, 195, 197, 199, 201, 203, 205, 206, 207, 209, 210, 211, 212, 214, 215, 216, 218, 220, 222, 223, 224, 225, 227, 229, 231, 233, 235, 236, 237, 239, 240, 242, 244, 245, 246, 248, 250, 252, 254, 255, 257, 259 260, 262, 264, 266, 268, 269, 270, 271, 272, 274, 276, 278, 279, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 305, 306, 307, 309, 311, 312, 314, 315, 316, 318, 320 321, 323 or 325, or a complement thereof;
• (b) a polynucleotide comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:
• 2, 8, 12, 14, 20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326;
• (c) a polynucleotide comprising a nucleotide sequence that encodes a polypeptide that shares at least 50% sequence similarity with at least a portion of the sequence set forth in SEQ ID NO:
• 2, 8, 12, 14, 20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326, wherein the portion comprises at least 15 contiguous amino acid residues of that sequence;
• and (d) a polynucleotide comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under at least low stringency conditions.

A kit comprising one or more endotoxemia marker polypeptides selected from the group consisting of:

• (i) a polypeptide comprising an amino acid sequence that shares at least 50% sequence similarity with the sequence set forth in any one of SEQ ID NO:
• 2, 8, 12, 14, 20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326;
• (ii) a polypeptide comprising an amino acid sequence that shares at least 50% sequence similarity with a polypeptide expression product of an endotoxemia marker gene that comprises a sequence set forth in anyone of SEQ ID NO:
• 2, 8, 12, 14,20, 22, 24, 28, 30, 32, 34, 36, 40, 46, 48, 51, 53, 55, 57, 59, 62, 65, 72, 74, 78, 85, 87, 89, 91, 95, 97, 99, 105, 108, 112, 116, 118, 120, 127, 129, 131, 133, 135, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 159, 161, 163, 165, 167, 171, 175, 177, 179, 181, 183, 185, 187, 189, 191, 196, 198, 200, 202, 204, 208, 213, 217, 219, 221, 226, 228, 230, 232, 234, 236, 238, 241, 243, 247, 249, 251, 253, 256, 258, 261, 263, 265, 267, 273, 275, 277, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 308, 310, 313, 317, 319, 322, 324 or 326;
• (iii) a portion of the polypeptide according to (i) or (ii) wherein the portion comprises at least 5 contiguous amino acid residues of that polypeptide;
• (iv) a polypeptide comprising an amino acid sequence that shares at least 30% similarity with at least 15 contiguous amino acid residues of the polypeptide according to (i) or (ii);
• and (v) a polypeptide comprising a portion of the polypeptide according to (i) or (ii), wherein the portion comprises at least 5 contiguous amino acid residues of the polypeptide according to (i) or (ii) and is immuno-interactive with an antigen-binding molecule that is immuno-interactive with a sequence of (i), (ii) or (iii), or the use of one or more antigen-binding molecules that are immuno-interactive with a said endotoxemia marker polypeptide, in the manufacture of a kit for diagnosing the presence of an endotoxemia-related condition in a subject.